Supporting Information for publication Middle-down hybrid chromatography/tandem mass spectrometry workflow for characterization of combinatorial post-translational modifications in histones Simone Sidoli§, Veit Schwämmle§, Chrystian Ruminowicz, Thomas A. Hansen§, Xudong Wu¶, Kristian Helin¶ and Ole N. Jensen§‡ § Centre for Epigenetics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark ¶ Centre for Epigenetics, Biotech Research and Innovation Centre, University of Copenhagen, DK-2200, Copenhagen, Denmark ‡To whom correspondence should be addressed: Prof. Ole N. Jensen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Tel: +45 6550-2368. Fax: +45 6550-2467. E-mail: jenseno@bmb.sdu.dk. Index 1) Supporting information abstract (page 2) 2) Results: optimization of MS/MS detection without dynamic exclusion (page 2) 3) Results: Histone Coder principle of operation and performance 4) Results: isoScale principle of operation and performance (page 3) 5) Results: comparison of histone H3 marks quantified in crude histone mixture and purified fraction (page 4) 6) Results: comparison of H3K27K36 results with previous publication of Jung et al. (MCP, 2010) (page 4) 7) Results and discussion: middle-down analysis of histone isotypes H3.2/H3.1 and H3.3 (page 5) 8) References (page 5) 9) Supplementary figures and tables – captions (page 6) 10) Supplementary figures and tables (page 8) 1) Supporting information abstract We provide here supporting data regarding the methodology we implemented for the middle-down proteomics workflow. We demonstrate, among others, that (i) by not using dynamic exclusion (DE) in the MS/MS acquisition method we obtained exhaustive identification of isobaric polypeptides, (ii) the deconvolution algorithm Xtract performs better for our workflow than other widely used ones, (iii) isoScale provides robust quantification independently of sample purity, (iv) our results are comparable with previous publication where bottom-up proteomics and SILAC labeling was adopted. 2) Results: optimization of MS/MS detection without dynamic exclusion We optimized the MS acquisition method to accurately map the PTMs along the peptide sequence and detect isobaric modified peptides. Extensive peptide sequence coverage by MS/MS is especially required for histone tails, as they have numerous potential modification sites; e.g. in histone H3, the PTMs ac and me3 potentially localize on 8 different K, while me1 and me2 on 14 sites between K and R. As previously demonstrated, ETD is the most suitable fragmentation technique for effective histone tail fragmentation in hybrid MS such as the LTQ-Orbitrap, due to its efficiency for long and heavily charged peptides such as histone tails [1, 2] (Fig. S3). The acquisition method was implemented to perform Data Dependent Acquisition (DDA), where the 6 most intense ions were selected at each MS cycle for MS/MS fragmentation, without adopting dynamic exclusion (DE). DE is commonly enabled to avoid repetitive selection of previously fragmented peptides, but it prevents the selection of isobaric peptides. We tested the acquisition method by analyzing the purified fraction of histone H3 of wild type and Suz12 -/- ESCs. From this analysis we identified 713 different histone H3 combinatorial marks (Table S3), which is currently an unmatched result in the entire literature for a single protein. This result overcame more than 6-fold our previous report, where we identified 114 combinatorial marks in ESCs with the same sample preparation, but different LTQ-Orbitrap (XL vs Velos) [2]. The 2 713 differently modified peptides identified had only 37 different nominal masses (approximated without decimal values), indicating that each precursor mass corresponded to almost 20 different PTMs patterns. Therefore, the use of DE is not recommended to identify isobaric peptides. 3) Results: Histone Coder principle of operation and performance The role of Histone Coder is to verify whether the PTM localization assigned by Mascot is supported by fragment ions present in the MS/MS spectrum. To do so, the software counts the number of `site determining ions´ between the assigned PTM localization and the two closest alternative sites. If ions are found, the Mascot assignment is considered unambiguous and certain. Mascot can provide up to 10 possible hits for each MS/MS spectrum; Histone Coder considers each of them separately and assigns site determining ions for all the PTM combinations provided by Mascot. In some cases, the MS/MS spectrum contains site determining ions for more than one hit (Fig. S5); this leads to the validation of multiple hits from the given spectrum. Spectra containing multiple hits validated by Histone Coder are candidates for isoScale quantification (see section 4). The principle of Histone Coder is similar to other proteomics tools such as PhosphoRS [3]. However, Histone Coder includes unique features that make it currently the only available tool for middle-down proteomics analysis. For example, Histone Coder offers a simple user interface, while other algorithms such as the mixed linear optimization framework developed in DiMaggio, et al. [4] are currently not available. Also, Histone Coder copes with multiple different PTMs residing within the same peptide sequence; other tools such as PhosphoRS [3], the A-score [5], the PTM-score [6] and the Mascot Delta score [7] are effective, but only for single modifications (mostly phosphorylation). The output of Histone Coder does not provide a probability score, but it includes all information about number and type of site determining ions detected in the MS/MS spectrum. In the output table the column named `Site determining ions´ lists the site determining ions for each assigned PTM (Fig. 2B and S10), while the column named `Modification confidence´ lists the number of site determining ions, type (e.g. c32, z41) and how many potential fragments could be detected. For instance, in figure S11A two over four ions were identified between R2 and K4 to localize the me1, which are c2 and (z+1)48; this last one was not mapped by Mascot, due to higher stringency applied during database searching to discriminate ac and me3. Eventually, a probability score can be calculated manually by the user based on the provided information. However, we recommend the use of the site determining ions column to filter for reliable hits; the probability score is calculated based on the number of potential fragment ions identified between two aa residues, but the ETD fragment ions of a histone tail do not have equal probability to be generated. Specifically, larger mass ions are less frequent than smaller ones, and c fragments are generally more frequent than z+1 or z+2 ones (Fig. S4 and S11). Therefore, PTMs in the high mass region (e.g. H3K27ac or H3K36ac) would result as generally less confident than PTMs in small mass region (e.g. H3K4ac or H3K9ac), even though they had sufficient fragment ions to prove their localization as unambiguous. 3 4) Results: isoScale principle of operation and performance isoScale was implemented to retrieve the data for peptide quantification directly from the Mascot output. The logo of isoScale was designed to metaphorically represent the ability of the software in performing relative quantification of isobaric peptides (Fig. S7A). To exploit the information of MS/MS spectra containing the fragments of multiple isobaric peptides we made isoScale able to extract from the Mascot .csv result file(s) the fragment ion relative ratio (FIRR) of two peptides differentially modified and fragmented in the same MS/MS spectrum. This file is the one we define as Data file. The Result file is the output of Histone Coder, where the ambiguous PTM assignments were removed. We recommend to not change the sorting of the table in the output of Histone Coder, as isoScale uses the two top-ranking identifications for each query, and the raw output is already sorted from higher to lower Mascot score. As previously demonstrated by Pesavento et al. [8] the intensity of the fragment ions can be adopted to estimate the relative abundance of different isobaric co-fragmented species. To do so, isoScale extracts the unique ions for each of the two identified peptides, where for `unique ions´ is intended all the fragment ions that univocally discriminate one peptide from the other. As illustrated in Figure S7B, an MS/MS spectrum might contain multiple isobaric histone tails (in the example, H3K9me3 and H3K4me1K9me2). The unique ions are the fragment ions included from K4 to A7, as they have different masses in the two species (R8 would be also a unique ion, but it was not identified). They are used by the searching engine to identify the two peptides. The FIRR is calculated by using the average FIRR of each individual fragment type (e.g. K4/K4*, Q5/Q5*, T6/T6*…). isoScale extracts this information, and it divides the total ion intensity of the MS/MS spectrum for such ratio, and it divides the intensity between the two species. To avoid coarse errors in the calculation of such ratio we included the option for fragment mass tolerance, which we recommend as <0.05 Da for high resolution data. In addition, we applied a filter for FIRR variability; once the software calculates the individual rations of the various fragment types (e.g. K4/K4*, Q5/Q5*, T6/T6*…) it generates the average and it calculates the coefficient of variation based on the individual FIRRs. In case such coefficient of variation exceeds 50% the ratio is considered as null and the total ion intensity is completely assigned to the top probable identification. This limit was integrated as Pesavento et al. proved that FIRR variability between individual fragment types is generally very small (estimated to be around 5% for species in 1:1 ratio) [8]. Therefore, highly variable FIRRs indicates erroneous calculation of the peptide relative abundance. Furthermore, isoScale is suitable for both CID and ETD spectra. Once the total ion intensity is extracted for each identified and validated peptide the total abundance of a given peptide is calculated by summing all total ion intensities obtained from all spectra where this peptide was identified (Fig. S7C). FIRR was calculated and the total ion intensity of each spectrum was then divided between the two cofragmented peptides. Total peptide abundance was calculated in the same manner (Fig. S7D). This approach overcomes the challenge of partially overlapping chromatographic profiles of two isobaric peptides; i.e. in spectra where the two peptides overlap, the total ion intensity is the sum of both co-fragmented peptides, differently the MS/MS spectrum total ion intensity corresponds to the fragmentation of a single peptide. In those cases where two peptides partially overlap the total abundance was calculated from MS/MS spectra using the FIRR correction and also from additional spectra where the peptide ion was isolated alone (Fig. S7E). 4 We assessed the performance of isoScale in the main text of the article (Fig. 3). In addition, we include here further details regarding the comparison between isoScale and spectral counting quantification. By analysing the three technical replicates of the purified histone H3 fraction from Suz12 -/- cells we quantified 357 combinatorial PTMs with isoScale and 239 with spectral counting, considering peptides detected in at least one of the three replicates. Despite the larger number of combinatorial marks identified both quantification strategies achieved a similar percentage of missing values, defining as missing value a combinatorial histone code not identified in one of the three technical replicates (1 missing value) or two of them (2 missing values). For isoScale 43.3% was the average missing values percentage in each of the three replicates, while for spectral counting it was 44.5%. This indicated that the higher amount of quantified peptides with isoScale is not due to sporadic identifications in one of the replicates, but it is a consistent improvement as compared to spectral counting. Linear regression analysis demonstrated that extracted ion chromatogram (XIC), which we used as reference, and isoScale results correlated better than XIC and spectral counting (Fig. S8A). On average, the variation of the quantification between spectral counting and XIC results was around 3-fold changes higher as compared to isoScale and XIC, indicating that isoScale provides absolute quantification more in line to XIC area integration. isoScale is freely available at: http://middle-down.github.io/Software/ 5) Results: comparison of histone H3 marks quantified in crude histone mixture and purified fraction Fewer steps of histone purification lead to simpler sample preparation and reduced variability of results. Furthermore, it leads to reduced sample loss, which might be crucial for the analysis of samples with low sample availability. Here, we briefly show that the results obtained from the analysis of purified histone H3 sample (starting material ~200 µg of histones) are comparable to the histone H3 quantification from the crude histone mixture, obtained directly from the TCA precipitation (starting material ~10 µg). For this aim we performed linear regression between the relative quantification achieved for single histone H3 marks from the analysis of the two samples (average of the technical replicates). We achieved high correlation (R2: 0.97 for wt experiment, 0.90 for Suz12-/-) (Fig. 5D). Moreover, we compared the relative abundance of the combinatorial marks that we identified in both analyses, and we observed a reduced, but not low, correlation (R2: 0.75 for wt, 0.62 for Suz12-/-). Finally, we compared the two sample preparation methods by first generating the ratio of wild type and Suz12-/- conditions. Specifically, we correlated the ratios (relative abundance Suz12-/- / relative abundance wild type) of the results obtained from the two sample preparations. We obtained an R2 of 0.72 for the analysis of single marks, and an R2 of 0.96 for the analysis of combinatorial marks, demonstrating that both analyses provide comparable results. For instance, by comparing the co-existence frequencies of H3K27 and H3K36 marks we obtained two highly similar results for both sample preparation analyses (Fig. S8C). In summary, we provide evidence that our workflow achieves comparable results independently from sample purity. 5 6) Results: comparison of H3K27K36 results with previous publication of Jung et al. (MCP, 2010) As further validation of our method, we investigated variations in abundance of H3K27 and H3K36 co-occurrences, due to the possibility to compare it with results previously obtained in our group [9]. In this previous work, we adopted traditional bottom-up proteomics using SILAC-MS [10], and spectra were acquired using both high and low resolution for MS/MS with CID and ETD. Results were for 50% in agreement with the previous analysis (Table S10), even though this previous analysis presented several differences with the middle-down strategy; the work of Jung et al. was much more focused on K27-K36 PTM co-existence, and it was different in terms of MS strategy and quantification method. For 5 combinatorial marks total agreement was found between the experiments, while in 5 cases a partial disagreement was found, mostly because in one of the two experiments less than 2-folds changes were observed between wild type and Suz12-/- cells. Furthermore, we characterized 9 combinatorial marks with the histone mixture analysis which we could not detect in the work in 2010. However, we found a significant difference in the quantification of K27ac, which we did not detect as increasing in Suz12-/- cells with the current middle-down analysis. The wild type/Suz12-/- ratio of this mark was found to be ~1, and no statistical difference was detected. Therefore, we conclude that our middle-down workflow provides results in line with previous publications, but results with the bottom-up strategy are still not completely correlated. 7) Results and discussion: middle-down analysis of histone isotypes H3.2/H3.1 and H3.3 Middle-down proteomics is potentially capable of discriminating highly similar histone isotypes, e.g. H3.2 / H3.3 or H2A type 1 / H2A.x, as the little differences in the amino acid sequence between these variants are included in the Nterminal tails. We did not highlight this aspect in the main article, as we rapidly verified that subdividing the results of the four canonical histones in their isotypes would have resulted in fewer data and poor statistics. However, we included a brief description of the analysis of single marks quantified in H3.2 and H3.3 (aa 31 A/S). We observed significant differences between single marks quantification in H3.2 and H3.3. In particular, we identified 10 marks out of 43 significantly different in terms of relative abundance in wild type, and 15 out of 43 in Suz12 -/- (Fig. S9 and Table S11). These marks were mainly low abundance ones such as H3K4 or H3K14/K18/K23 methylations. However, we also identified H3K9me3 as significantly different between H3.2 and H3.3 in Suz12-/- cells (6.16% for H3.2, 22.36% for H3.3). In summary, our middle-down workflow is potentially suitable to investigate differences in single and combinatorial marks residing on the N-terminal tails of histone isotypes such as H3.2 and H3.3. 8) References [1] Mikesh, L. M., Ueberheide, B., Chi, A., Coon, J. J., et al., The utility of ETD mass spectrometry in proteomic analysis. Biochim Biophys Acta 2006, 1764, 1811-1822. [2] Jung, H. R., Sidoli, S., Haldbo, S. N., Sprenger, R. R., et al., Precision mapping of co-existing modifications in histone H3 tails from embryonic stem cells by ETD-MS/MS. Anal Chem 2013. [3] Taus, T., Kocher, T., Pichler, P., Paschke, C., et al., Universal and Confident Phosphorylation Site Localization Using phosphoRS. Journal of Proteome Research 2011, 10, 5354-5362. 6 [4] DiMaggio, P. A., Young, N. L., Baliban, R. C., Garcia, B. A., Floudas, C. A., A Mixed Integer Linear Optimization Framework for the Identification and Quantification of Targeted Post-translational Modifications of Highly Modified Proteins Using Multiplexed Electron Transfer Dissociation Tandem Mass Spectrometry. Molecular & Cellular Proteomics 2009, 8, 2527-2543. [5] Beausoleil, S. A., Villen, J., Gerber, S. A., Rush, J., Gygi, S. P., A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature Biotechnology 2006, 24, 1285-1292. [6] Cox, J., Neuhauser, N., Michalski, A., Scheltema, R. A., et al., Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment. Journal of Proteome Research 2011, 10, 1794-1805. [7] Savitski, M. M., Lemeer, S., Boesche, M., Lang, M., et al., Confident Phosphorylation Site Localization Using the Mascot Delta Score. Molecular & Cellular Proteomics 2011, 10. [8] Pesavento, J. J., Mizzen, C. A., Kelleher, N. L., Quantitative analysis of modified proteins and their positional isomers by tandem mass spectrometry: Human histone H4. Analytical Chemistry 2006, 78, 4271-4280. [9] Jung, H. R., Pasini, D., Helin, K., Jensen, O. N., Quantitative Mass Spectrometry of Histones H3.2 and H3.3 in Suz12-deficient Mouse Embryonic Stem Cells Reveals Distinct, Dynamic Post-translational Modifications at Lys-27 and Lys-36. Molecular & Cellular Proteomics 2010, 9, 838-850. [10] Ong, S. E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., et al., Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Molecular & Cellular Proteomics 2002, 1, 376-386. [11] Wilkins, M. R., Gasteiger, E., Bairoch, A., Sanchez, J. C., et al., Protein identification and analysis tools in the ExPASy server. Methods Mol Biol 1999, 112, 531-552. 9) Supplementary figures and tables – captions Figure S1. Histone H3 purification and analysis. (A) Three aligned UV chromatograms representing elution of intact histones from C18 column, specificity of purified H3 fraction and reproducibility. The purification of histone H3 was performed three times to verify reproducibility in separation and retention time of the various intact histone isotypes. The drift in the retention time was around 1 min at maximum between the three replicates. R.T. = retention time. (B) emPAI Mascot quantification of the proteins identified in the fraction underlined in (A). Quantification percentage highlights the high purity of histone H3. (D) Three LC-MS runs from wild type sample of the purified histone H3 tails. Highly acetylated peptides are eluted first. At minutes ~10 and ~20 shorter peptides are eluted baseline resolved from histone tails; their relatively higher intensity was cut off the picture for a better visualization. Figure S2. in-silico GluC digestion of histone H3, H4 and canonical H2A performed by PeptideMass [11]. Histone Nterminal peptides are the largest peptides generated by endoproteinase Glu-C digestion. Note: Only peptides with no missed cleavage sites and with a mass higher than 500 Da were allowed. Figure S3. MS/MS spectra and deconvolution. ETD and HCD performance were investigated via direct infusion. ETD (A) and HCD (B) fragmentation of the peptide ARTKQTARKSTGGKAPRKQLATKAARKSAPATGGVKKPHRYRPGTVALRE + 2 methyl groups and respective spectra deconvolution with Xtract (on the right). The figure shows a lower efficiency of HCD fragmentation (normalized collision energy 35) as compared to ETD. Figure S4. Deconvoluted and annotated spectra. (A) Fragmentation and c/z ions annotation of the unmodified histone H3 tail. (B) Fragmentation of the N-terminal acetylated histone H4. (C) Fragmentation of the N-terminal acetylated histone H2A. c ions were commonly more present than z ions. On the right side of the spectra the most intense peaks represent the non-fragmented precursor ions with respective neutral losses. Figure S5. Histone Coder performance for deconvoluted mixed MS/MS spectra. (A) Spectrum containing two histone H3.2 peptides modified as K27me1 and K36me1. (B) Same spectrum deconvoluted by Xtract. (C) Zoom into the 7 deconvoluted spectrum in the region where site determining ions are located. The ions characterizing H3K27me1 are highlighted in blue, while ions characterizing H3K36me1 are highlighted in orange. The annotation is only for the five ions of the same type detected for both peptides. The fragment ions of the two peptides show a delta mass of 14 Da. (D) Output of the Histone Coder. The two peptides were both identified by Mascot, but with different confidence and score. However, both were found as reliable by counting the number of site determining ions. In particular, Histone Coder detected 14 fragment ions confirming me1 localization in K27 instead of K36 (row 2, column 6), and 9 ions confirming me1 in K36 instead of K27 (row 3, column 6). Figure S6. Histone H4 and H2A PTM quantification. Quantified PTMs of histones H4 (A) and H2A (B). On the X axis, modification positions. Modification type is violet: trimethyl (me3), light blue: dimethyl (me2), green: monomethyl (me1), red: acetyl (ac). On the Y axis, fraction of occupied site on the total histone quantified. Figure S7. isoScale principle of operation. (A) Logo of the software. (B) MS/MS spectrum of two isobaric peptides. The black symbols represent the fragments of the species K9me3, the red ones the species K4me1K9me2. (C) Principle of quantification for a peptide where no co-fragmented isobaric species where found. The total abundance is calculated by summing all the calculated total ion intensity from each peptide-spectrum match (PSM). (D) Quantification of two isobaric peptides co-eluted. For each MS/MS spectrum the FIRR was calculated (marked as an asterisk *) and the total ion intensity was divided by the two co-fragmented peptides before calculating the total abundance. (E) Example of partially overlapping peptides. The FIRR was calculated only for the MS/MS spectra where the two species where found as co-fragmented. Figure S8. isoScale performance. (A) Correlation with XIC quantification for each of the three replicates analyzed. Data refer to the 22 groups of peptides generated for comparison with XIC (Fig. 3). Results show a higher correlation between reference (XIC) and isoScale quantification than spectral counting. (B) Correlation of single (left) and combinatorial (right) marks quantification between the sample containing the crude histone mixture and the one with purified histone H3. (C) H3K27K36 co-occurrence frequency. Connector lines describe the difference in abundance of the binary marks between the two cell lines. Green lines represent higher abundance in wt, while red lines in Suz12-/-. Thicker lines represent higher difference. Figure S9. Histone H3 isotypes H3.2(H3.1) and H3.3. Abundance of the histone marks identified on the canonical histone H3 tail (H3.2) and the isotype H3.3. Modification type is violet: trimethyl (me3), light blue: dimethyl (me2), green: monomethyl (me1), red: acetyl (ac). On the Y axis, fraction of occupied site on the total histone quantified. Figure S10. Mascot assignment of me3/ac in searches with MS/MS tolerance set as 0.05 Da. MS/MS annotated spectrum of the histone H3 N-terminal tail modified. Almost every fragment peak resulted as matching theoretical fragmentation (represented with green dashed lines). Below, delta mass distribution of the different fragment ions between theoretical and observed masses, expressed in Dalton (top) and ppm (bottom). (A) Wrong assignment of K9me3, underlined by the constant delta mass of +0.03 Da for the c ion series, starting from the mass corresponding to the ion c9. (B) Correctly assigned acetylation. By imposing a product ion tolerance of 0.05 Da the search engine 8 could not discriminate two modifications which differ of only 0.03 Da. For both hits on the same spectrum the same ion score and expect value was assigned. Figure S11. Annotated spectra. Mascot graphical output of annotated spectra for (A) K4me1K9me2K14acK18acK23acK27me2K36me2, which is the most heavily modified peptide detected, (B) K9me2K27acK36me3, the lowest scoring peptide which passed bioinformatics validation (Mascot score: 0), (C) K14me3 and (D) K18me3. On the right, the theoretical fragment ions for each hit. The numbers in bold red are the ones matching with observed fragment ions in the MS/MS spectrum. Below, the output of the Histone Coder for the four hits. In the column Modification confidence few more ions are present than the ones in bold red. This is due to the 30 ppm tolerance for searching site determining ions adopted by Histone Coder, which is more tolerant than 0.01 Da adopted by Mascot. Table S1. Retention time of histone tails in four technical replicates. Retention time (in min) and coefficient of variation (% CV) of six groups of peptides. Specifically, we reported the begin and the end of the elution profile for the injection peak, the short peptides (1-2 kDa), the medium length peptides (3 kDa) and the histone N-terminal tails for the histone H3, H4 and H2A. Table S2. Relative quantification of histone H3 N-terminal tails grouped for number of PTM equivalents. The table contains the values adopted to generate the figure 3A in the main article. Table S3. Relative abundance of combinatorial histone H3 marks obtained from the purified histone H3 analysis. The list of combinatorial histone marks quantified in wild type and in Suz12 -/- ESCs was obtained from six replicates. The relative abundance is calculated by summing the quantification of the same peptide in all six replicates, and then dividing it by the total amount of histone H3 N-terminal tail quantified. B.D.L. = below detection limit. Table S4. Relative abundance of combinatorial histone marks from histone H3. Quantified combinatorial PTMs detected in the crude histone mixture. The results were obtained from four technical replicates. Table S5. Relative abundance of binary histone marks from histone H3 achieved from the analysis of the purified histone H3 fraction. The t-test column represents the calculated p-value from an homoscedastic t-test one tail. Table S6. Relative abundance of binary histone marks from histone H3 achieved from the analysis of the crude histone mixture. The t-test column represents the calculated p-value from an homoscedastic t-test one tail. Table S7 and S8. Relative abundance of combinatorial histone marks from histone H4 and H2A. Quantified combinatorial PTMs detected in the crude histone mixture. The results were obtained from four technical replicates. Table S9. Output example of decoy database searching. Mascot output of searches that included decoy search for validation. No middle-down spectra matched a scrambled histone database by chance. Table S10. Comparison bottom-up and middle-down. Result comparison between data obtained in our previous work*, and our current analysis performed for the purified histone H3 fraction and the histone mixture. WT and 9 Suz12-/- cells indicate that the co-occurrence is more abundant in wild type cells or Suz12-/-, respectively. White cells represent less than 2-fold changes regulation. Unmodified sites (unmod) are also considered. Table S11. Relative abundance of histone marks identified on histone H3.2 and H3.3. Significant changes were calculated with t-test (5%, one tail, paired). In green, the histone marks detected as significantly changing between histone H3.2 and H3.3 within the same cell condition. 10 Figure S1 (A) (B) H4 H2B H2A H3.2 H3.3 H1 H3.1 H3 isolated fraction >99% specificity R.T. shift 3 replicates 1 min (C) RT: 0.00 - 130.00 NL: RT: 0.00 -9.39E7 130.00 Base Peak MS Obv03151 Shorter peptides RT: 0.00 - 130.00 3 Ac 2 Ac 1 Ac NL: 9.39E7 NL: Peak Base 9.86E7 MS Base Peak Obv03151 MS obv03152 O Ac NL: 9.86E7 NL: Peak Base 1.01E8 MS Base Peak 7000000 obv03152 MS obv03153 6000000 7000000 6000000 5000000 NL: 1.01E8 4000000 Base Peak MS 3000000 obv03153 Intensity Intensity 5000000 4000000 7000000 3000000 6000000 Intensity 2000000 5000000 2000000 1000000 4000000 0 3000000 1000000 0 10 20 30 40 50 60 70 Time (min) 80 70 60 Time (min) 80 90 100 110 120 1000000 0 0 10 20 30 40 50 0 0 2000000 11 90 100 110 120 10 20 30 40 Figure S2 12 Figure S3 (A) Obv02123 #2827 RT: 95.78 AV: 1 NL: 4.31E3 T: FTMS + p NSI d sa Full ms2 673.90@etd22.50 [100.00-2000.00] Obv02123_XT_00001_MHp_ #2 RT: 2.00 AV: 1 NL: 7.63E3 T: FTMS + p NSI d sa Full ms2 673.90@etd22.50 [100.00-2000.00] 832.46 z=2 100 1074.83 z=5 1343.28 z=4 90 95 90 895.52 z=6 474.31 z=1 85 85 80 80 75 75 70 65 55 1010.92 z=3 45 719.89 z=2 40 35 983.17 z=5 1286.25 z=4 1148.66 z=3 45 4080.33 40 3442.97 35 205.60 288.14 443.78 z=? z=? z=? 346.22 z=? 157.94 z=? 1414.15 z=3 1538.57 z=3 529.83 z=2 1912.81 z=? 1638.61 z=3 2355.38 3029.74 25 20 3720.20 1941.15 30 245.17 z=1 25 5 50 573.34 651.36 z=2 z=2 30 4910.81 55 Xtract 770.17 z=7 50 60 Relative Abundance Relative Abundance 1361.47 z=3 1229.21 z=4 60 10 1663.92 70 65 15 5339.08 100 ETD 95 828.50 1145.68 20 602.37 4680.71 15 1715.00 z=3 1791.71 z=3 10 1945.56 z=? 3895.25 3314.91 2069.21 997.59 475.32 2625.54 4454.55 5 0 5138.96 4239.46 1438.77 1303.75 3131.80 0 200 400 600 800 1000 1200 1400 1600 1800 2000 500 1000 1500 2000 2500 3000 m/z 3500 4000 4500 5000 m/z (B) H3 HCD test_001 #209 RT: 3.00 AV: 1 NL: 2.77E4 T: FTMS + p NSI Full ms2 674.20@hcd30.00 [140.00-1500.00] H3 HCD test_001_XT_00001_MHp_ #2 RT: 2.00 AV: 1 NL: 2.85E4 T: FTMS + p NSI Full ms2 674.20@hcd30.00 [140.00-1500.00] 673.89 z=? 100 767.91 z=2 1534.82 100 HCD 95 95 90 90 85 85 80 80 75 75 674.40 70 70 65 747.44 z=? 60 55 55 Xtract 50 45 40 35 60 Relative Abundance Relative Abundance 65 631.37 z=3 211.12 z=1 703.39 z=2 50 45 35 842.47 z=1 30 30 25 25 20 15 842.47 40 776.42 z=2 165.44 z=? 10 603.68 z=3 228.14 z=? 287.13 z=? 346.22 z=? 385.12 z=? 870.01 z=4 776.42 2290.29 15 1003.06 1053.59 z=2 z=? 5 1159.51 z=? 1302.76 1808.04 1406.78 637.38 10 1248.32 z=? 3047.82 1662.91 20 517.95 457.27 z=3 z=? 5 0 0 200 300 400 500 600 700 800 m/z 900 1000 1100 1200 1300 1400 1500 13 400 600 800 1000 1200 1400 1600 m/z 1800 2000 2200 2400 2600 2800 3000 Figure S4 obc04466_xt_00001_mhp_ #2 RT: 2.00 AV: 1 NL: 1.35E5 T: FTMS + p NSI d w Full ms2 668.64@etd22.50 [100.00-2000.00] (A) 100 95 90 c16 85 Histone H3 80 75 70 c4 Relative Abundance 65 60 55 50 45 c18 40 c10 35 c6 30 25 c7 20 c5 15 c12 c 13 c28 c22 c17 c8 c19 c11 10 z46 c36 c21 c14 c24 c20 5 c32 z31 c31 c27 c26 c35 c43 c44 c41 z45 c47 z48 0 500 1000 1500 2000 2500 3000 3500 4000 4500 5000 m/z Obc04462_XT_00001_MHp_ #2 RT: 2.00 AV: 1 NL: 1.46E5 T: FTMS + p NSI d w Full ms2 721.68@etd22.50 [100.00-2000.00] (B) 100 95 90 85 Histone H4 80 75 70 Relative Abundance 65 60 55 50 c13 45 40 35 30 25 20 15 10 c10 c3 c5 c7 c6 c8 c23 c 26 c14 c 15 c c16 17 c12 0 500 obc04463_xt_00001_mhp_ #2 1000 RT: 2.00 AV: 1 1500 NL: 1.25E6 T: FTMS + p NSI d w Full ms2 564.57@etd22.50 [100.00-2000.00] 100 z37 z38 c29 c30 c24 c22 c19 5 c32 c34 2000 z45 c35 2500 3000 m/z 3500 4000 4500 z47 z48 5000 5500 (C) 95 90 85 80 Histone H2A 75 70 Relative Abundance 65 60 55 50 45 40 35 30 25 c4 20 15 10 c5 c c8 6 z20 c c24 c16 c7 c9 23 c21 c11 c c14 z9 c12 13 c15 c17 c19 c20 z22 z21 z33 c27 c28 z30 c33 z32 5 0 500 1000 1500 2000 2500 m/z 14 3000 3500 4000 4500 Figure S5 (A) (B) Obv02119 #3308 RT: 116.43 AV: 1 NL: 2.89E4 T: FTMS + p NSI d sa Full ms2 670.27@etd22.50 [100.00-2000.00] Obv02119_XT_00001_MHp__140429121930 #2 RT: 2.00 AV: 1 NL: 5.10E4 T: FTMS + p NSI d sa Full ms2 670.27@etd22.50 [100.00-2000.00] 5311.07 5353.09 832.47 z=2 100 100 95 1069.02 z=5 90 95 90 85 1053.86 z=? 893.52 z=6 80 85 474.31 z=1 80 5296.05 75 766.16 z=7 70 1663.92 75 70 65 5356.10 4881.79 5267.04 5252.01 5110.93 4895.82 4953.86 4066.37 4196.40 4210.43 4372.56 4427.55 4439.53 4581.65 4653.69 4682.71 4753.73 5367.10 3691.17 3414.95 4053.35 3868.24 3916.32 3995.34 3700.15 3428.96 3563.08 3707.20 2873.62 2731.55 2482.49 2624.55 3001.72 1941.16 1303.75 5 3248.91 3285.88 3349.97 10 2345.30 15 1945.56 z=? 3014.73 3088.74 1705.33 1781.37 1890.21 z=3 z=3 z=? 2069.21 2113.22 1552.90 z=3 1948.11 1434.16 z=3 177.05 z=? 0 100 1628.94 z=3 2254.34 5 1404.81 z=3 529.83 z=2 1912.86 z=? 1607.91 10 465.78 288.14 z=2 z=? 346.22 401.23 z=? z=? 982.55 25 20 226.55 z=? 15 602.37 751.78 765.59 774.46 30 20 1656.96 35 1279.24 z=4 903.52 930.56 245.17 z=1 1792.01 40 924.05 z=4 2354.38 45 1139.66 z=3 30 25 50 245.17 35 55 475.32 573.35 648.06 z=2 z=3 719.89 z=2 40 60 1813.06 977.56 z=5 1488.87 1329.53 z=4 739.24 z=5 45 1664.94 50 1145.68 1221.96 z=4 1438.78 55 Relative Abundance Relative Abundance 65 60 0 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000 500 1000 1500 2000 2500 3000 m/z 3500 4000 4500 5000 m/z 2069.21 Obv02119_XT_00001_MHp__140429121930 #2 RT: 2.00 AV: 1 NL: 6.73E3 T: FTMS + p NSI d sa Full ms2 670.27@etd22.50 [100.00-2000.00] me1 (C) 100 (z+1)18 ARTKQTARKSTGGKAPRKQLATKAAR K S A P A T G G V K KPHRYRPGTVALRE 95 c28 90 c31 c32 c33 (z+1)18 85 me1 ARTKQTARKSTGGKAPRKQLATKAAR K S A P A T G G V K KPHRYRPGTVALRE 80 3001.72 Obv02119_XT_00001_MHp__140429121930 #2 RT: 2.00 AV: 1 NL: 1.38E4 T: FTMS + p NSI d sa Full ms2 670.27@etd22.50 [100.00-2000.00] c28 65 50 45 40 (z+1)18 25 60 20 55 15 (z+1)18 50 2020 2040 2060 2080 2100 2120 25 2140 m/z 2160 5 c33 3363.96 3299.87 10 c31 3234.91 3218.87 3115.79 3088.74 15 2180 c33 c31 c28 20 c32 3392.98 c28 3272.85 30 0 2000 3248.91 35 c32 3285.88 5 3014.73 40 2986.70 10 45 2177.21 2179.77 30 65 3400.93 2005.13 2006.20 35 70 0 3000 3050 3100 3150 3200 m/z 3250 3300 3350 3400 (D) Mascot score Expection value Scan number Histone code Run name Site det. ions 129.77 5.7E-12 3308 K27me1 WT rep3 |2-K27me1-14| 111.53 3.8E-10 3308 K36me1 WT rep3 |9-K36me1-3| 15 3406.97 75 3349.97 80 55 3335.95 85 2082.25 2084.22 90 2113.22 60 2019.15 95 Relative Abundance c31 c32 c33 70 Relative Abundance 100 75 2200 2220 Figure S6 (A) H4 Suz12-/- relative occupancy H4 Wild type S1 S1 (B) H2A Suz12-/- relative occupancy H2A Wild type S1 K125 16 S1 K125 Figure S7 Obv02232_XT_00001_MHp_ #2 RT: 2.00 AV: 1 NL: 2.18E3 T: FTMS + p NSI d sa Full ms2 683.77@etd22.50 [100.00-2000.00] (B) 474.31 (A) 100 K4 me3 A R T K Q T A R K … 95 me2 A R T K Q T A R K … 602.37 85 80 1100.70 me1 90 K9-K9* Q5 75 774.46 70 65 A7 K4* 1085.13 1010.60 1021.60 1022.97 959.56 967.57 5 984.60 995.59 769.45 T6* 801.79 718.44 10 600.36 571.33 15 918.04 A7* 20 934.07 Q5* 842.52 25 859.52 865.86 30 1024.36 1030.61 1063.42 1064.88 1068.63 866.19 T6 T3 827.85 839.98 35 616.39 40 346.22 45 897.53 703.42 50 877.84 895.14 903.54 488.33 55 788.47 Relative Abundance 60 0 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 m/z (D) Peptide with no isobaric species 400 500 peptide 1 peptide 2 350 300 250 206 200 150 100 50 0 Retention time TOTAL Calculated total ion current (arbitrary units) Calculated total ion current (arbitrary units) 450 (E) Co-eluting isobaric peptides 500 457 450 peptide 1 400 peptide 2 350 300 250 206 200 150 * 100 50 0 * * * * * * * Retention time * * * TOTAL 500 Calculated total ion current (arbitrary units) (C) 450 400 Partially co-eluting isobaric peptides 457 peptide 1 350 300 250 206 200 150 * 100 50 0 * * * * Retention time *a single MS/MS spectrum, where the FIRR between peptide 1 and 2 was calculated 17 peptide 2 * * * TOTAL Figure S8 (A) (B) Single marks Replicate 1 Spectral counting 0.57 isoScale 1 0.90 Replicate 2 0.61 0.69 Replicate 3 0.66 0.88 R2 correlation R2 0.97 0.9 0.75 0.5 0.25 0 Wild type Suz12-/- Histone mixture 18 0.75 0.62 0.5 0.25 Purified H3 1 0.75 0 (C) Combinatorial marks Wild type Suz12-/- relative occupancy relative occupancy H3.3 relative occupancy H3.2 relative occupancy Figure S9 wild type Suz12-/- 19 Figure S10 (A) (B) 20 Figure S11 (A) (B) (C) (D) Figure Histone code A K4me1K9me2K14acK18acK23acK27me2K36me2 B K9me2K27acK36me3 C K14me3 D K18me3 Site determining ions Modification confidence K4me1{R2:2/4(c:2;z+1:48;)-R8:4/8(c:4;c:5;c:6;z+2:45;)} K9me2{R8:2/2(c:8;z+2:42;)K14:9/10(c:10;c:11;c:12;c:13;z+2:37;z+2:38;z+2:39;z+2:40;z+2:41;)} K14ac{K9:9/10(c:10;c:11;c:12;c:13;z+2:37;z+2:38;z+2:39;z+2:40;z+2:41;)P16:1/4(z+1:36;)} K18ac{P16:4/4(c:16;c:17;z+2:33;z+2:34;)K23:8/10(c:18;c:19;c:21;c:22;z+2:28;z+2:29;z+2:31;z+2:32;)} |2-K4me1-4||2-K9me2-9||9-K14ac-1||4-K18ac-8| K23ac{K18:8/10(c:18;c:19;c:21;c:22;z+2:28;z+2:29;z+2:31;z+2:32;)|8-K23ac-8||3-K27me2-12||12-K36me2-2| K27:8/8(z+1:24;z+2:24;c:23;c:24;z+1:26;z+2:26;z+1:27;c:26;)} K27me2{R26:3/2(z+1:24;z+2:24;c:26;)K36:12/18(z+1:16;z+1:17;z+1:18;z+2:18;z+1:19;z+2:23;c:27;c:28;c:32;c:33;c :34;c:35;)} K36me2{K27:12/18(z+1:16;z+1:17;z+1:18;z+2:18;z+1:19;z+2:23;c:27;c:28;c :32;c:33;c:34;c:35;)-K37:2/2(z+1:14;c:36;)} K9me2{R8:2/2(c:8;z+1:42;)K14:6/10(c:10;c:11;c:13;z+1:37;z+2:39;z+2:41;)} K27ac{K23:1/8(z+1:26;)|2-K9me2-6||1-K27ac-1||3-K36me3-2| P30:1/6(c:27;)} K36me3{K27:3/18(z+1:15;z+2:18;c:27;)K37:2/2(z+1:14;z+2:14;)} K14me3{K9:6/10(c:10;c:12;c:13;z+2:37;z+1:40;z+2:41;)|6-K14me3-6| K18:6/8(c:14;c:16;c:17;z+1:33;z+2:34;z+2:36;)} |4-K18me3-10| 21 K18me3{K14:4/8(c:14;c:16;c:17;z+2:34;)K23:10/10(c:18;c:19;c:20;c:21;c:22;z+1:28;z+2:28;z+1:29;z+1:31;z+1:32;)} Table S1 Injection peak 1-2 kDa peptides 3 kDa peptides histone H3 tails histone H4 tails histone H2A tails histone H2B tails replicate 1 begin 5.6 18.8 29.1 87.8 89.9 97.8 111.3 end 11.3 29.1 84.8 126.0 141.9 124.4 125.7 replicate 2 begin 5.5 18.8 28.8 88.2 98.7 97.6 110.8 end 11.0 28.8 84.2 125.7 137.3 125.3 126.5 replicate 3 begin 5.5 18.7 29.1 89.6 101.4 96.0 109.7 Table S2 PTMs unmod 1me 2me 3me 4me 5me 6me 7me 8me 9me 1ac 1ac1me 1ac2me 1ac3me 1ac4me 1ac5me 1ac6me 2ac 2ac1me 2ac2me 2ac3me 3ac XIC 1.88% 1.62% 5.02% 9.98% 14.01% 14.82% 8.59% 2.49% 0.33% 0.00% 1.73% 1.81% 4.02% 6.18% 8.52% 7.07% 4.30% 1.28% 1.32% 2.09% 2.93% 0.00% Spectral counting 8.01% 4.27% 9.60% 16.68% 15.32% 8.98% 4.92% 1.54% 0.16% 0.14% 3.21% 2.28% 4.58% 5.31% 7.08% 4.25% 1.01% 0.62% 0.50% 0.65% 0.77% 0.12% isoScale 3.10% 1.90% 4.47% 11.19% 16.18% 9.69% 8.66% 2.69% 0.07% 0.09% 3.38% 1.80% 3.37% 5.57% 12.88% 6.28% 3.41% 0.77% 1.39% 1.51% 1.47% 0.14% 22 end 11.2 29.1 84.5 126.6 139.2 127.0 125.4 replicate 4 begin 5.5 18.7 29.3 88.7 103.2 94.9 108.8 end 11.1 29.3 84.5 125.4 138.6 125.3 128.0 % CV begin 1.05% 0.17% 0.71% 0.91% 6.01% 1.43% 1.03% % CV end 1.16% 0.71% 0.33% 0.40% 1.40% 0.87% 0.90% Table S3 Histone code Wild type Suz12-/- Histone code Wild type Suz12-/- Histone code Wild type Suz12-/- K9me1K14me1K27me2K36me2 12.23% 1.69% K9acR17me2K27me2K36me2 0.34% 0.23% K4me3K23acK27me2K36me2 0.04% B.D.L. K27me2K36me2 9.31% B.D.L. K23acK27me3 0.16% 0.05% K9acK14me1K18acK23acK27me2K36me2 0.04% B.D.L. K9me1K27me2K36me2 8.39% B.D.L. K14acK18acK23acK27me2K36me2 0.11% B.D.L. K18acK27me2K36me2 0.04% B.D.L. K9me3K27me2K36me2 6.19% 1.68% K4me1K9me1K18acK23acK27me2K36me2 0.11% B.D.L. R17me1R26me1K36me2 0.04% B.D.L. K9me1K14me1K23acK27me2K36me2 4.30% 0.18% K14acK27me3K36me3 0.10% B.D.L. K4me1K23acK27me2K37me1 0.04% B.D.L. K23acK27me2K36me2 3.95% 0.02% K18me1K23me1K27me1K36me2 0.10% B.D.L. K9me2K14acK18acK23acR42me2R49me2 0.04% B.D.L. K9me1K23acK27me2K36me2 2.99% B.D.L. K9me1K14me1K27me3K36me2 0.10% B.D.L. K9me1K14acK18acK23acK27me3 0.04% B.D.L. K27me2K36me1 1.72% 0.01% K9me2K23me3K27acK36me1K37me1 0.10% B.D.L. K9me2K27me3R40me1 0.04% B.D.L. K23acK27me2K36me1 1.56% 0.15% K14me1R17me1K27me2K36me2 0.10% B.D.L. K9me1K36me3 0.04% B.D.L. (unmodified) 1.41% 3.01% K14me1K18acK23acK27me2K36me2 0.10% B.D.L. K4me1K9me1K14acR17me1K23acR26me1K27me1K36me1K37me1 0.04% B.D.L. K9me2K27me3K36me1 1.32% 0.04% K9me3K23me2K27me2K36me2 0.09% B.D.L. K9me2K27me3R49me2 0.04% K14acK18acK27me2K36me2 1.27% B.D.L. K14me1K18me1K23acK27me2K36me2 0.09% B.D.L. K9me2K14acK18acK23acK27me1K36me1K37me1 0.04% B.D.L. K9acK14me1K18me1K23acK27me2K36me2 1.26% B.D.L. K14acK23me3R26me1K27me3 0.09% B.D.L. K23acK27ac 0.05% 0.01% K9me1K14acK27me2K36me2 1.17% B.D.L. K9acK18me1K23me2K27me2K36me2 0.09% B.D.L. K27me1K36me3 0.04% B.D.L. K9me3K14acK27me2K36me2 1.95% 0.81% K9me2K23me3K27ac 0.09% B.D.L. K18me1K27me2K36me2 0.04% B.D.L. K27me3K36me2 1.08% B.D.L. K9me2K14acK18me1K23me1K27acK36me3 0.08% B.D.L. R8me1K9acR17me1K23me2R26me1K27me2K36me2 0.04% B.D.L. K9me3K23acK27me2K36me2 1.02% B.D.L. K18me1K23me1K27acK36me2 0.08% B.D.L. R8me1K14acK27me2K36me2 0.03% B.D.L. K9me1K14acK18acK27me2K36me2 0.90% B.D.L. K4me1K9me1K14acK23acK27me3K36me1K37me1 0.08% B.D.L. R17me2K27me2K36me2 0.04% 0.00% K9me3K14acK18acK27me2K36me2 0.87% B.D.L. K9me2K14acK23me3K27me1K36me1K37me1 0.08% B.D.L. K9me1K14me1R26me1K27me2K36me2 0.03% B.D.L. K14acK18acK27me2 1.12% 0.28% R26me1K27me1K36me1 0.08% B.D.L. K4me3K27me2K36me2 0.03% B.D.L. K9me2K27me3K36me1K37me1 0.80% 0.03% K27me2R40me2 0.08% B.D.L. K14acK18me2K23acK27me1K36me1 0.03% B.D.L. K27me1K36me2 1.04% 0.28% K9me2K18acR26me2R40me2 0.07% B.D.L. K9me3R26me1K27me2K36me2 0.04% 0.00% K23acK27me2 1.03% 0.28% K9me3K27me2K36me1K37me1 0.16% 0.08% K9me2K23me1K27me1K36me3 0.03% B.D.L. K14acK18me1K23acK27me2 0.71% B.D.L. K9acK14me1K18acK27me2K36me2 0.07% B.D.L. K9me3R26me2K27me1K36me1K37me1 0.03% B.D.L. K14me1K27me2K36me2 0.59% B.D.L. K4me1R8me1R17me1K27me2K36me2 0.07% B.D.L. K14acK18me1K23acK36me3 0.03% B.D.L. K9me1K14me1K18acK27me2K36me2 0.58% B.D.L. K18acK23acK27me2K36me1 0.07% B.D.L. K23acR26me1K36me3 0.03% B.D.L. R8me1K9me1K14me1K27me2K36me2 0.58% 0.05% K9me2K23acK27me3 0.07% B.D.L. K9me1K27me2R40me1R42me1 0.03% B.D.L. K23me1K27me1K36me2 0.51% B.D.L. K9me2K18acK23acK27me1K36me1K37me1 0.07% B.D.L. K9me3K23me2R26me2K27me2K36me2 0.03% B.D.L. K14acK27me2K36me2 0.48% B.D.L. R8me1K9me1K23me2K27me2K36me2 0.07% B.D.L. K9me2K18acK27me3 0.03% B.D.L. R8me1K9me1R17me1K27me2K36me2 0.39% B.D.L. K23acK27me3K36me1K37me1 0.07% B.D.L. K4me1K27me2K36me2 0.03% B.D.L. K23acR26me1K27me2K36me2 0.39% B.D.L. R8me2K14acK18acK27me2K36me2 0.07% B.D.L. K9me1K18acK23acK27me3 0.03% B.D.L. K9me1R17me1K27me2K36me2 0.35% B.D.L. K9me3K18acK23acK27me2K36me2 0.07% B.D.L. R8me1K23acK27me1K36me1K37me1 0.03% B.D.L. K9me1K14acK18acK23acK27me2K36me2 0.34% B.D.L. K9me3K14me3K27me2K36me2 0.07% B.D.L. K9acK23me3K27me3K36me2 0.03% R26me1K27me2K36me2 0.33% B.D.L. K4me1K9me1K18acK27me2K36me2 0.08% 0.01% R26me2K27me1K36me1K37me1 0.03% B.D.L. K23acR26me1K27me1K36me1 0.32% 0.01% K9me1K14acK23me2K27me2K36me2 0.07% B.D.L. K4me1K9me1K14acK18acK23acK27me2K36me2 0.07% 0.04% K9me3K18acK27me2K36me2 0.34% 0.05% K14acK18acK27me3 0.07% B.D.L. K4me2K23acK27me3K36me1K37me1 0.03% B.D.L. K23acK27me2K36me3 0.28% B.D.L. K9acK27me2K36me2 0.06% B.D.L. K23acK27me1K36me3 0.03% B.D.L. K27me1K36me1 0.32% 0.05% K9me1K23acK27me3 0.06% B.D.L. K4acR8me1K27me2K36me2 0.03% B.D.L. K9me1K23acK36me3 0.26% B.D.L. K14acK18acR26me1K27me1K36me1 0.06% B.D.L. K14acR17me1K18acK27me2K36me2 0.03% B.D.L. K9me1K18acK23acK27me2K36me2 0.26% B.D.L. K23acK27me2K36me1K37me1 0.06% B.D.L. K9acK14acK23me2R26me1K27me2K36me2 0.03% B.D.L. K27me3 0.45% 0.20% K27me3K36me1K37me1 0.06% B.D.L. K9me3K14me3K23acK27me2K36me2 0.03% B.D.L. K9me3K14acK18acK23acK27me2K36me2 0.24% B.D.L. R8me2K18acK27me2K36me2 0.08% 0.02% K9me1K14acK18acK36me3 0.03% B.D.L. K9acK14me1K18me1K27me2K36me2 0.23% B.D.L. K9acR17me1K27me2K36me2 0.06% B.D.L. K14acK18me2K23acK27me3 0.03% B.D.L. K9me2K27me3R40me2 0.22% B.D.L. K14acK18me1K23me1K27ac 0.06% B.D.L. K9me1K18acK23me2K27me2K36me2 0.03% B.D.L. R8me2K14acK23me2K27me2K36me2 0.21% B.D.L. K27me2K36me3 0.06% B.D.L. K18acK23acK27me1K36ac 0.03% B.D.L. K4me1K23acK27me2K36me2 0.20% B.D.L. R8me2R26me1K27me2K36me2 0.06% B.D.L. R17me1K18acK27me2K36me2 0.03% B.D.L. K14acK23me3K27me2K36me2 0.20% B.D.L. K9me2K23acK27me1K36me1K37me3 0.06% B.D.L. K18acK23acK27me3 0.03% B.D.L. K14acK23me3K27me3 0.20% B.D.L. K9me2K23me3K27me3K36me1 0.06% B.D.L. R17me1K23me2K27me2K36me2 0.03% B.D.L. K4me1K9me1K27me3K36me2 0.19% B.D.L. K14acK27me1 0.06% B.D.L. K14acK23me1K27me1K36me2 0.03% B.D.L. K14acK18me1K23acK27me2K36me2 0.19% B.D.L. K9me2K23acK27acR49me2 0.06% B.D.L. R26me1K36me1 0.03% 0.01% K14acK18me1K23me2K27ac 0.17% B.D.L. K23acR26me2K27me1K36me1 0.06% B.D.L. K9me1K14me1K23me2K27me2K36me2 0.02% B.D.L. R26me2K36me2 0.15% B.D.L. K4me1K9me1R26me1K27me2K36me2 0.06% B.D.L. K9me1K18acK23acK27me2 0.02% B.D.L. K9me1K14me1K18acK23acK27me2K36me2 0.15% B.D.L. K14acK23me2K27me3 0.06% B.D.L. K9acK14me1K18acK23acK27me3 0.02% B.D.L. K18acK23acK27me2K36me2 0.14% B.D.L. K4me3K14acK27me2K36me2 0.06% B.D.L. K18acK23acK27acK36me2 0.02% B.D.L. K14acR17me2K27me2K36me2 0.22% 0.08% K9me3K27me2K36me2K37me1 0.07% 0.02% K9me2K23me3K27me3 0.02% B.D.L. K14me1K23acK27me2K36me2 0.14% B.D.L. K9me2K23acK27me1K36ac 0.14% 0.09% K14acK18acK23acK27me1K36me3 0.02% B.D.L. K14acK23me3K27me2 0.14% B.D.L. K4me1K9me1K23acK27me2K36me2 0.08% 0.03% R8me1K14acR17me1K18acK27me3 0.02% B.D.L. K4me1K9acK23acK27me2K36me1K37me1 0.13% B.D.L. K4me1K9me2K23acK27me3K36me1K37me1 0.05% B.D.L. K9acK14me3K27me2K36me2 0.02% B.D.L. K27me3K36me1 0.13% B.D.L. R8me1K23acK27me2K36me2 0.05% B.D.L. K4acK9me1K36me3 0.02% B.D.L. R8me2K18acK23acK27me2K36me2 0.13% B.D.L. R8me1K27me2K36me2 0.05% B.D.L. K9me2K14acK18acK23acK27me1K36me1K37me3 0.02% B.D.L. K9me2K27me3R40me1R42me1 0.13% B.D.L. K5acK15me1 0.11% 0.06% K9me1R26me1K36ac 0.02% B.D.L. R8me1K18acK23acK27me2K36me2 0.12% B.D.L. K18acK23acK27me2 0.10% 0.05% K9me3K23acK27ac 0.02% B.D.L. K14acK18acK27me1 0.36% 0.24% K9acK23me3K27me2K36me2 0.05% B.D.L. K4me1K9me1K14acK27me3K36me1K37me1 0.02% B.D.L. K9acK14me1K27me2K36me2 0.12% B.D.L. K27me2R49me2 0.05% B.D.L. K14acK23me3K27me1 0.09% 0.07% K4me1K9me1K14acK23acK27me2K36me1K37me1 0.12% B.D.L. K14acK18acK27me2K36me1 0.05% B.D.L. K14acK27me2 0.02% B.D.L. K9acK14me1K18me1K23me1K36me2 0.12% B.D.L. R17me1K27me2K36me2 0.05% B.D.L. R26me2K36ac 0.02% B.D.L. K9me2K23acR42me2R49me2 0.13% 0.02% K18me1K23me1K36me2 0.05% B.D.L. K14acK23me3K27me3K36me1 0.02% B.D.L. K4me1K9me2K27me3K36me1K37me1 0.11% B.D.L. K9me1K23me2K27me2K36me2 0.05% B.D.L. K4me1R8me1K9me1K27me3K36ac 0.02% B.D.L. K4me1K9me1K14me1K27me3K36me2 0.11% B.D.L. K14acK18acK23acK27me2 0.05% B.D.L. K9acK23me2R26me2K27me2K36me2 0.02% B.D.L. K27me2K36me1K37me1 0.11% B.D.L. K9me1R26me1R42me2 0.04% B.D.L. K9acK14acK23me2K27me2K36me2 0.02% B.D.L. K18me3K36me2 0.02% B.D.L. K14me3K18acK23acK27me2K36me2 0.01% B.D.L. K5acR17me1 0.00% 0.00% K9me1R26me1K36me3 0.02% B.D.L. K20ac 0.01% B.D.L. R17me1R26me2K27ac B.D.L. 0.00% R17me1K23acK27me2K36me2 0.02% B.D.L. K9me2K27me3R49me1 0.01% B.D.L. K23acR49me1 B.D.L. 0.00% K23acR26me2K36me3 0.02% B.D.L. K27me3R40me2 0.01% B.D.L. K9me2R17me1K36me3 B.D.L. 0.00% K23acR26me2R40me2 0.02% B.D.L. K27me1R42me2 0.01% B.D.L. K4me1K36me2 B.D.L. 0.00% K4acK27me3 0.02% B.D.L. K9me1K14acK36me3 0.01% B.D.L. K23acR49me2 B.D.L. 0.00% K9me2K27me1K36me3 0.61% 0.59% K14acK36me1 0.01% B.D.L. K9me3K14me3K18acK36me2 B.D.L. 0.00% K9acK14me2K18acK23acK27acR42me2 0.02% B.D.L. K9me3K14me1K18me3K27me2K36me2 0.01% B.D.L. K9me1K14acK18acR26me2 B.D.L. 0.00% K9me2K18acK23acK27me3 0.02% B.D.L. K23acK27me1K36ac 0.01% B.D.L. R26me2 B.D.L. 0.00% K23acK27me2K36ac 0.02% B.D.L. K23acK37me2 0.01% 0.00% K14acK36me2 0.00% 0.01% 23 B.D.L. B.D.L. Table S3 - continues Histone code Wild type Suz12-/- Histone code Wild type Suz12-/- Histone code Wild type Suz12-/- K14acK18me2K23me2K27me1K36ac 0.02% B.D.L. K9acK18me2K23me2K27me2K36me2 0.01% B.D.L. K18acK27me1K36me1K37me1 B.D.L. 0.00% K4me3K27me2K36me1 0.02% B.D.L. K18acK36me1 0.01% 0.00% K9me2K18acK27me1 B.D.L. 0.00% K9me2K27acR40me2 0.02% B.D.L. K4me1K14acK18acK23acK27acK36me2 0.01% B.D.L. K9me2K23acR26me2R40me2 0.02% 0.03% K14acK18acK23me1K27me2 0.02% B.D.L. K27me2R42me2 0.01% B.D.L. K9me3R49me2 B.D.L. 0.00% K9me2K18me1K23me1K36me3 0.02% B.D.L. R17me1R26me1K27me1K36me1 0.01% B.D.L. K23me3K36me2 0.00% 0.01% K14acK18acK23acK27me1 0.02% B.D.L. K27me3R40me1 0.01% B.D.L. K9me2K23me1K36me3 B.D.L. 0.00% K9me1K23me3K27me2K36me2 0.02% B.D.L. K9me1K14me2K27ac 0.01% B.D.L. K9me3K36me2K37me2 B.D.L. 0.00% K14acK18me1K23me2K27me2K36me2 0.02% B.D.L. K14acK18acK23acK36me2 0.01% B.D.L. K23me2K36me1 B.D.L. 0.00% K14me1K18me1K27me2K36me2 0.01% B.D.L. K9me1K27me3 0.01% B.D.L. K9me3K23me1K36ac B.D.L. 0.00% K9acK14me1K18acK23me2K27me2K36me2 0.01% B.D.L. K18acK23me1K27me1K36me1 0.01% B.D.L. K9me1R26me2 B.D.L. 0.00% K14acK18me2K23acK36me1K37me1 0.01% B.D.L. K4me1K9me1K23acK27me3K36me1K37me1 0.01% B.D.L. R17me1K27me1 B.D.L. 0.00% K14acK18acR26me1K27me2K36me2 0.01% B.D.L. K9me3K27me2K36ac 0.00% B.D.L. K9acK14me3K18me3K36me2 B.D.L. 0.00% K14acK18acR26me2R40me2 0.01% B.D.L. K14acK23me1K27me1K36me1 0.00% B.D.L. K9me2K23me1R49me2 B.D.L. 0.00% K14acK18me2K23me1K27ac 0.01% B.D.L. K27me3K37me2 0.00% B.D.L. K18acK27me1 0.01% 0.01% K9acK23me3K27me3 0.01% B.D.L. K18acK27me2 0.00% B.D.L. K9me2K27acR49me2 0.02% 0.03% K23acK27me2K37me3 0.01% B.D.L. K14me3K27me2K36me1 0.00% B.D.L. K9me2K27me3K36ac B.D.L. 0.01% K14acR26me1K27me1K36me1 0.01% B.D.L. K18acK23acR26me1K27me3 0.00% B.D.L. K9me2R26me2K36me1 0.00% 0.01% K23acK27acK36me1 0.01% B.D.L. K23acR26me2K36me1 0.00% B.D.L. K4me1K9me2K14acK27me1K36me1K37me1 B.D.L. 0.01% K14acK18me2K23acK36me3 0.01% B.D.L. K27me1R49me2 0.00% B.D.L. K9me1K14me1R40me1R42me1 B.D.L. 0.01% K9me3K18me2K23me2K27me2K36me2 0.01% B.D.L. K18acK23acK36me2 0.03% 0.02% K9me2K23ac B.D.L. 0.01% K18acK23me3K27me1 0.01% B.D.L. K9me1K23me2R26me1K27me2K36me2 0.00% B.D.L. K14me1R17me2 B.D.L. 0.01% K4me1K14acK18acK23acK27me2K36me2 0.01% B.D.L. K23me3K27me3K36me2 0.00% B.D.L. K23me3K36ac B.D.L. 0.01% K18me1K23acK27me2K36me2 0.01% B.D.L. K23me2K27acK36me1 0.00% B.D.L. R42me1 B.D.L. 0.01% K9me1K18acK27me2K36me2 0.01% B.D.L. R26me1K27me1R40me2 0.00% B.D.L. K4me1K9me1K23acK27me1K36me1K37me1 B.D.L. 0.01% K14acK23me2R26me1 0.01% B.D.L. R26me1K27me1 0.01% 0.00% K9acK36me3 B.D.L. 0.01% K23me1K27me2K36me2 0.01% B.D.L. K9me1R26me1K27me3 0.00% B.D.L. K9me2K23me1K36ac B.D.L. 0.01% K9me1K23acK27acR42me1R49me1 0.01% B.D.L. K27me3R42me1 0.00% B.D.L. K9me2K14acK18acK23acR49me2 B.D.L. 0.01% K9me1K14acK27me3 0.01% B.D.L. K9me2K23acK27acR40me2 0.00% B.D.L. R17me2 B.D.L. 0.01% K18acK23me3K27me3 0.01% B.D.L. K9me1K18acK27me2 0.00% B.D.L. K9me2K18me1K36me3 B.D.L. 0.01% K9acK14acK18me1K23me1K27acK36me2 0.01% B.D.L. K14acK18me1K27me2 0.00% B.D.L. R8me2K23acK27me2K36me2 0.06% 0.06% K14acK27me2K36me1 0.01% B.D.L. K4me1R8me1K27me2K36me2 0.00% B.D.L. R8me1K9me1K36me3 B.D.L. 0.01% R8me1K23me1K36me3 0.01% B.D.L. K23acR26me2K27me1K36me1K37me1 0.00% B.D.L. K14me2K27me1K36me1 B.D.L. 0.01% K4me1K9acK36me2 0.01% B.D.L. K18acK27me3K36me3 0.00% B.D.L. K9me2K37me3 B.D.L. 0.01% K14acK18acK36me1 0.01% B.D.L. K18acR26me1K27me2K36me2 0.00% B.D.L. R17me1K23me1K27me1K36ac B.D.L. 0.01% K14acK18acR26me2K36me3 0.01% B.D.L. K14me3K36me2 0.00% B.D.L. K9me3K18acK27me1K36me1K37me1 B.D.L. 0.01% K9me3K27acK36me1K37me1 0.01% B.D.L. K23me3 0.00% 0.00% K9me3K23acK27me2K36ac B.D.L. 0.01% K9me1K14me1K18me1R26me1K27me2K36me2 0.01% B.D.L. K18acK23acR26me1K27me1K36me1 0.00% B.D.L. K14me3K23acK27me1K36me1K37me1 B.D.L. 0.01% K4me1K9me1K14acK23acK27me1K36me2K37me1 0.01% B.D.L. K23me2K27ac 0.00% B.D.L. R17me1K23acR26me2 B.D.L. 0.01% R26me1K27me1K36me1K37me1 0.01% B.D.L. K14acK18me1 0.00% B.D.L. K9me1K14me1 B.D.L. 0.01% K9me2K37me1R49me2 0.01% B.D.L. K23acK27me1K37me3 0.00% B.D.L. K9me2K14acK27me1 B.D.L. 0.01% K14me3K23acK27me2K36me2 0.01% B.D.L. K14acK23me1 0.00% B.D.L. K9me2K14me2R17me1 B.D.L. 0.01% K23acK37me3 0.01% B.D.L. K27me2K37me1 0.00% B.D.L. K9me1K23acR42me1R49me1 B.D.L. 0.01% K15me1 0.20% 0.19% R26me1K27me2 0.01% 0.01% K9me1R40me2 B.D.L. 0.01% K23me2K27me2K36me2 0.01% B.D.L. K9acR49me2 B.D.L. 0.00% K9me1K23me2K27me2 B.D.L. 0.01% K14acR17me1K27me1K36me1 0.01% B.D.L. K9me2K14me1K36ac B.D.L. 0.00% K4me1K9me2K18acK36me3 B.D.L. 0.01% R17me1K23acK27me1K36me1 0.01% B.D.L. K14me2R42me2 B.D.L. 0.00% K36me1K37me1 0.00% 0.01% K14acK18acK23acK27me3 0.01% B.D.L. R49me1 B.D.L. 0.00% K9ac 0.00% 0.01% K9me1K18acK23me2K27ac 0.01% B.D.L. K9me1R40me1R42me1 B.D.L. 0.00% K9me1K14acR17me1K18acK23ac B.D.L. 0.01% K27me1R40me1 0.01% B.D.L. K9me2K23acK37me1 B.D.L. 0.00% K18me1K23me1K27me1K36ac B.D.L. 0.01% K14acK18me2K23acK36me1 0.01% B.D.L. K4ac B.D.L. 0.00% R26me1K36me1K37me1 B.D.L. 0.01% K4me1K18acK23acK27me2K36me2 0.01% B.D.L. K9me1K14acR17me1 B.D.L. 0.00% K9me2K14acK18acK23acR40me2 B.D.L. 0.01% K9me1K23acK27me2K36ac 0.01% B.D.L. K9me2K14me1K36me3 B.D.L. 0.00% K37me2 B.D.L. 0.01% K14acK18acK27me2K36me1K37me1 0.01% B.D.L. K18me1K23ac B.D.L. 0.00% K9me2K23acK27ac 0.01% 0.01% K14me1K18acK27me2K36me2 0.01% B.D.L. K23acK27acK36me2 0.02% 0.02% R8me1K14acK18me1K23me1K27ac B.D.L. 0.01% K14acK18acK23acK27me2K36me1 0.01% B.D.L. K18me2K23ac B.D.L. 0.00% K9me1K14me1K18me1K23me1K27acK36me2 0.00% 0.01% K9me2K18acK23me3K27ac 0.01% B.D.L. K9me2R17me1 B.D.L. 0.00% K4me1K9me1K14acK27me1K36me1K37me1 B.D.L. 0.01% K27acR40me2 0.01% B.D.L. K18acK36me2 0.00% 0.00% K18me1K23acR26me2 B.D.L. 0.01% R8me1K14acK18acK23me1K27me1K36me1 0.01% B.D.L. K18acK23me1 B.D.L. 0.00% K4me2K23acK27me1K36me3 B.D.L. 0.01% K14acR26me2K27me1K36me1 0.01% B.D.L. K18me3K36ac B.D.L. 0.00% K9me2K18acK23acK36me3 B.D.L. 0.01% K9me1K14me1K18acK23acK36me2 0.11% 0.10% R17me2K23acK27me2K36me2 0.01% 0.01% K9me2K27acR42me2 B.D.L. 0.01% K14me2 B.D.L. 0.01% K9me3K23me2R26me2K27me2 B.D.L. 0.03% K23me1 0.01% 0.07% K9me2K14me1R40me1R42me1 B.D.L. 0.01% R8me1R17me1K27me1 B.D.L. 0.03% K9me2K18acK36me1K37me1 B.D.L. 0.06% K9me3K37me2 B.D.L. 0.01% K4me1K9me1K14acR17me1K18acK23acK36me3 B.D.L. 0.03% K4me1K18acK36me2 B.D.L. 0.06% K9me2K23me1K27me3 B.D.L. 0.01% K9me2K18ac B.D.L. 0.03% K4me1K9me1K18acK27me1K36me1K37me1 B.D.L. 0.06% K9me2K27acK36me3 B.D.L. 0.01% K14acK23me3 0.09% 0.11% K9acK14me2K18acK27me1 B.D.L. 0.06% K4me1K9me1K14me1K23acK27acK36me2 B.D.L. 0.01% K23acK27me1K36me1 0.07% 0.09% K9me1K14acK18ac B.D.L. 0.06% K9me2K14acK18acR49me2 B.D.L. 0.01% K9me1K14me1K23acK27acK36me2 B.D.L. 0.03% K9me2K18acK36me3 B.D.L. 0.06% R17me1K27me3 B.D.L. 0.01% K4me1R8me1K9me1R17me1K27me2K36me2 B.D.L. 0.03% K18me3 0.03% 0.09% K9me3K14ac B.D.L. 0.01% R26me1K36me2 0.02% 0.05% K9me2K18acK23acK36me1K37me1 0.00% 0.07% K9me2K18acR49me2 B.D.L. 0.01% K9me1K14acK18acR40me2 B.D.L. 0.03% R17me1 0.04% 0.11% K14me2K27me1 B.D.L. 0.01% K9me2K27acK36me1K37me1 0.01% 0.03% K9me2K23me1 B.D.L. 0.07% K9acK14me2K36me1 B.D.L. 0.01% K4me2K14me1K23acK36me3 B.D.L. 0.03% K9me2K18acK23acK27me1K36me1 B.D.L. 0.07% K9me2R26me1K36me1R40me1 B.D.L. 0.01% K9me2R26me1K27me1K36me1R40me1 B.D.L. 0.03% R26me1 B.D.L. 0.07% K27acK36me1 B.D.L. 0.01% K9me2K18acK27me1K36me1 B.D.L. 0.03% K23me2 0.00% 0.07% K9me3K14me3K23acK36me2 B.D.L. 0.01% K9me2K18acK23acR26me2 B.D.L. 0.03% K9me2R26me1K36me1K37me1 B.D.L. 0.08% K9me2K23acR26me2 B.D.L. 0.01% K9acK36me2 B.D.L. 0.03% K4me1K14acK36me2 B.D.L. 0.08% R17me2K23acK27ac B.D.L. 0.01% R17me2K18acK27me2K36me2 0.04% 0.07% K4me1K9me1K36me2 B.D.L. 0.08% R17me2K18me1 B.D.L. 0.01% K9me3R26me2K27me2K36me2 B.D.L. 0.03% K18me1K23me1K27me1 B.D.L. 0.08% 24 Table S3 - continues Histone code Wild type Suz12-/- Histone code Wild type Suz12-/- Histone code Wild type Suz12-/- K4me1K9me2K36me3 B.D.L. 0.01% K9me2K14acK18acK23acK27me1K36me1 B.D.L. 0.03% K9me2K23acK37me3 B.D.L. 0.08% K4me1K9me3K27me2K36me2 B.D.L. 0.01% R8me1K23acK27me2 B.D.L. 0.03% K9me1K14me1K27acK36me2 B.D.L. 0.08% K9me2K36me3K37me1 B.D.L. 0.02% K9me3K36me1 B.D.L. 0.03% R40me2 B.D.L. 0.08% K9me2K23me1K27me1K36ac B.D.L. 0.02% K9me2K14acK18me1K23me1K27me1 B.D.L. 0.03% R17me2K36me2 B.D.L. 0.08% R17me1K36me1 B.D.L. 0.02% K23acR26me1 B.D.L. 0.03% K9me1K14me1K18me1K23acK36me2 B.D.L. 0.08% K23me3K37me2 B.D.L. 0.02% K9me1K14me1K23acR40me1 B.D.L. 0.03% K9me1K14ac B.D.L. 0.08% K9acK14me2K18acK23acK36me3 B.D.L. 0.02% K14me1K18me1K23acK36me2 B.D.L. 0.03% K9acK14me2K27me1K36me1 B.D.L. 0.08% K4me1K9me1R17me1K27me2K36me2 B.D.L. 0.02% K9me2K23me1K27me1K36me1K37me1 B.D.L. 0.03% K14acR17me1K18me1K23ac B.D.L. 0.08% K23acK27me1K36me1K37me1 0.02% 0.04% K9me2K27me1K36me1R49me1 B.D.L. 0.03% K14acK18acR26me1 0.01% 0.09% K9me1K14acR42me1R49me1 B.D.L. 0.02% K9me3K14me3K36me2 B.D.L. 0.03% K9acK14acK18me1K23me1K27me1K36me2 B.D.L. 0.08% R8me1K9me1K27me2 B.D.L. 0.02% K14me2K23acK36me1 B.D.L. 0.03% R17me1K23me1K27ac B.D.L. 0.08% K9me2R40me1 B.D.L. 0.02% K9me2K36me1R42me1 B.D.L. 0.04% K9me1K18me2 B.D.L. 0.08% K9me3K23acK36me1K37me1 B.D.L. 0.02% K4me1R8me1K9me1K14acK23acK27me1K36me1K37me1 B.D.L. 0.04% K9me2K14acK23me3K27me3 B.D.L. 0.09% K9me3K14acK23me2K27me2K36me2 0.19% 0.21% R42me2 B.D.L. 0.04% K14me2K36me1 B.D.L. 0.09% K18me1K36me2 B.D.L. 0.02% K9me2K18acK23me1K27ac B.D.L. 0.04% K9me3K27me2 B.D.L. 0.09% K4me1K9me1K14me1K36me2 B.D.L. 0.02% K9me2K18acR42me2 B.D.L. 0.04% K4me1K9me1K27me2K36me2 B.D.L. 0.09% K9acK14me1K18me1K23me1K27ac B.D.L. 0.02% K4me1K9me1K14me1K23acK36me2 B.D.L. 0.04% K9me2K14acK18ac B.D.L. 0.09% K9acK14me3K18acK23acK27me2 B.D.L. 0.02% K9me3K36ac B.D.L. 0.04% K9acK18me1K23me1K27me1K36me2 0.01% 0.10% K9me1K23me2K36ac B.D.L. 0.02% K4me1R8me2K27me2K36me2 0.01% 0.05% K9me2R17me1K36me1 B.D.L. 0.09% K36ac 0.02% 0.04% K9me2K27acK36me1 B.D.L. 0.04% K9me2K27me1R49me2 0.02% 0.11% K9me2K14me3 B.D.L. 0.02% K9me2K14acK37me3 B.D.L. 0.04% K4me1R8me1K9me1K18acK36me3 B.D.L. 0.09% K9me2R26me1K36me3 B.D.L. 0.02% K9me3K27me1K36me1K37me1 B.D.L. 0.04% K4me1K9me1K18acK36me2 B.D.L. 0.09% R17me1R26me2K36ac B.D.L. 0.02% K23acK36me1K37me1 0.01% 0.05% K9me1R17me1K23ac B.D.L. 0.09% K9me1K14me1K18me1K36me2 0.03% 0.05% K9me1K14acR40me2 B.D.L. 0.04% K9me2K14acK18acK27me1 B.D.L. 0.09% K9me2K37me1R40me1 B.D.L. 0.02% K9me2K18me1 B.D.L. 0.04% K9me2K14acK23me3 B.D.L. 0.09% K9me2 B.D.L. 0.02% K9me2K23me3K36ac B.D.L. 0.04% K9me2R26me1K27me1R40me1R42me1 0.02% 0.11% K9me2K18acR40me2 B.D.L. 0.02% K9me2K14me1K23me3K36ac B.D.L. 0.04% K4me1K9me1K18acR26me1K36me3 B.D.L. 0.10% K23acR26me1R40me2 B.D.L. 0.02% K9me2K14acK18acR42me2 B.D.L. 0.04% K9me2R26me1K27me1K36me1K37me1 0.07% 0.17% R49me2 0.00% 0.02% R17me2K18acK23acK27me2K36me2 B.D.L. 0.04% K9me2R49me2 B.D.L. 0.10% K14acR26me1 B.D.L. 0.02% K9me3K14acK18acK36me1K37me1 B.D.L. 0.04% K9me1K23me2 B.D.L. 0.11% K23me1K36me2 0.01% 0.03% K9me1K14me1K23ac B.D.L. 0.04% K9me3K27me2K36me1 0.02% 0.13% K9acK14me1R17me1K18acK23ac B.D.L. 0.02% K4me3K9me3K36me2 B.D.L. 0.04% K9me2K27me1 B.D.L. 0.11% K9me2K27me1R42me2 B.D.L. 0.02% K9me1K14acK27me2 0.01% 0.06% K36me1 0.26% 0.37% K9me2K14ac B.D.L. 0.02% R8me2K36me2 B.D.L. 0.05% K9acK14me1K18me1K23ac B.D.L. 0.11% K9me2R49me1 B.D.L. 0.02% K9me2K23acR42me1 B.D.L. 0.05% K4me1K9me2K14acK23acK27me1K36me1K37me1 B.D.L. 0.11% K4me1K9me2K27me3K37me1 B.D.L. 0.02% K14me1K23ac B.D.L. 0.05% K23acK36me3 0.05% 0.16% K9me1K18ac B.D.L. 0.02% K5ac 0.05% 0.10% K9me3K23acK27me1K36me1K37me1 B.D.L. 0.12% K18acK23acK27me1 0.11% 0.13% R17me1K36me2 B.D.L. 0.05% K9me2K36me1R40me1 B.D.L. 0.12% K9me1K14me1R26me1K36ac B.D.L. 0.02% K9me2K37me1R42me1 B.D.L. 0.05% K9me2K18acK36me1 B.D.L. 0.12% R8me2K36me1 B.D.L. 0.02% K18acK23ac 0.05% 0.10% K27ac 0.04% 0.16% K9me2K18acK23me1K27me1K36me1K37me1 B.D.L. 0.02% K4me1 B.D.L. 0.05% K14me1K36me2 0.00% 0.12% R8me2K27me2K36me2 0.09% 0.11% K14me1 B.D.L. 0.05% K9me1K14me1K18me1 B.D.L. 0.12% K9me3K27me1K36ac B.D.L. 0.02% R8me2K14acK27me2K36me2 0.08% 0.13% K9me2K23acK27acK36me1 B.D.L. 0.12% K4me2K14acK18acK27me1K36me1K37me1 B.D.L. 0.03% K9me1K23acR40me1 B.D.L. 0.05% K9me2K27me1K36ac B.D.L. 0.12% K9me2K14me1 B.D.L. 0.03% R8me1R17me1K36me1 B.D.L. 0.05% K9me2K18acK23acK36me1 B.D.L. 0.12% K9me2K27me1R40me1R42me1 B.D.L. 0.03% K14acK18acK36me2 B.D.L. 0.05% K9me1R17me2 B.D.L. 0.12% K9me2K14acK23me3K27me1K36me1 B.D.L. 0.03% K9acK14me2K18acK23ac B.D.L. 0.05% R8me1K9me2 B.D.L. 0.13% K9me2K14acK18acK36me1 B.D.L. 0.03% K9me3K36me1K37me1 B.D.L. 0.05% K9me2K23acK27me1 B.D.L. 0.13% K18me2 B.D.L. 0.03% K4me1K18acK23acK36me2 B.D.L. 0.05% K9me1K14me1R17me1 B.D.L. 0.13% K4me1K9me1K14acK23acK27me1K36me1K37me1 B.D.L. 0.03% K27acK36me2 0.07% 0.13% K9me2K14acK23me1K27me1K36me1K37me1 B.D.L. 0.14% K9me2K27me1K36me1R42me1 B.D.L. 0.03% K14me2R17me1 B.D.L. 0.06% K14me1K18me1K36me2 0.01% 0.15% K9me2R40me1R42me1 B.D.L. 0.03% K9me3K14acK27me1K36me1K37me1 B.D.L. 0.06% K9acK14me1K18me1K36me2 B.D.L. 0.14% K23acK27me1 0.42% 0.57% K14me3 0.02% 0.34% R8me1K9me1K27me2K36me2 3.98% 4.73% K9acK14me3K18acK23acK27me1K36me1 B.D.L. 0.15% K4me1K9me1K23acK36me2 B.D.L. 0.33% K14acK18me2K23ac B.D.L. 0.79% R8me1R17me1K36me2 B.D.L. 0.15% K9me2K23acR40me2 B.D.L. 0.33% K9acK14me1K18me1K23acK36me2 0.04% 0.87% K4me1K9me1K14me1K18acK36me2 B.D.L. 0.15% K23acK36me1 0.04% 0.37% K4me1K23acK36me2 B.D.L. 0.83% K9me2K27me1K36me1R40me1 B.D.L. 0.16% K4me1K9me2K14acK36me3 B.D.L. 0.33% K9me2K14acR40me2 B.D.L. 0.91% K9me1K23ac B.D.L. 0.16% K4me1K9me1K14acK36me2 B.D.L. 0.35% K9me2R40me2 B.D.L. 0.94% K18me1 0.01% 0.17% K9me2K14acK18acK27me3 B.D.L. 0.36% K4me1K9me1K14acK27me2K36me2 0.20% 1.14% K14acK18acK23ac 0.01% 0.18% K9me1K14acK18acK27me2 0.13% 0.49% K9me2K14acK36me1K37me1 B.D.L. 0.95% K27me1 0.35% 0.52% K4me1K9me1K14acK18acK27me2K36me2 B.D.L. 0.38% K9me2K23acK27me1K36me1K37me1 0.08% 1.05% K9me2R17me1K36me1K37me1 B.D.L. 0.17% K9me2R26me1K27me1K36me1 B.D.L. 0.39% K9me2K23acK36me1 B.D.L. 1.00% K36me3 0.01% 0.18% K4me1K9me1K14acK18acK36me2 B.D.L. 0.40% K9me2K14acK27me1K36me1 B.D.L. 1.13% K9me2K23acR49me2 B.D.L. 0.18% K9me1K23acK27me2 0.06% 0.47% K9me2K23acK36me1K37me1 B.D.L. 1.14% K9me2K14acR42me2 B.D.L. 0.18% K9me2K23acR42me2 B.D.L. 0.43% K9me2K27me1R40me2 0.06% 1.21% K9me2K27me3 0.05% 0.23% K14acK18ac 0.12% 0.57% K23acK36me2 0.36% 1.75% K9me2K14acK27me3K36me3 B.D.L. 0.19% K9me2K14acK36me1 B.D.L. 0.48% K9me2K36me1 B.D.L. 1.42% K9me2K18acK23acK27me1 B.D.L. 0.19% K9me2K14acK18acR40me2 B.D.L. 0.48% K9me2K23acK27me1K36me1 B.D.L. 1.61% K9me1 B.D.L. 0.19% K9me1K14me2 B.D.L. 0.48% K9me3K36me2 0.05% 1.69% K9me2K14acK18acK36me3 0.03% 0.23% K9me1K27me2 B.D.L. 0.50% K9me2K23acK36me3 0.01% 1.67% K4me1K9me1K14me1K27me2K36me2 0.06% 0.27% K27me2 0.64% 1.18% K9me2K36me1K37me1 B.D.L. 1.78% R8me1K36me2 B.D.L. 0.21% K9me2K14acK18acK27me1K36me1 0.04% 0.58% K36me2 1.05% 2.93% K9me2K36ac B.D.L. 0.23% K9me2R42me2 B.D.L. 0.54% K9me1K14me1K23acK36me2 0.01% 2.09% K9me1K23acR40me2 B.D.L. 0.24% K9me2K18acK27me1K36me1K37me1 0.02% 0.60% K9me3 0.09% 2.19% K9me2K14acK18acK23acK36me1 B.D.L. 0.25% K9me2K14acK18acK27me1K36me1K37me1 0.02% 0.60% K9me2K36me3 0.22% 2.68% K9me2K14acK18me1K23acK27ac B.D.L. 0.26% K9me2K14acK27me1K36me1K37me1 0.07% 0.67% K9me2K27me1K36me1K37me1 0.26% 2.76% K9me1K14me1K18acK36me2 B.D.L. 0.27% K9me2K14acK36me3 B.D.L. 0.63% K9me2K27me1K36me1 B.D.L. 2.70% K18ac 0.03% 0.31% K14ac 0.06% 0.70% K9me1K36me2 0.00% 3.80% R8me1K23acK27me1K36me1 B.D.L. 0.28% K14acK18me1K23ac 0.04% 0.70% K9me1K14me1K36me2 0.08% 9.01% K9me2K14acR49me2 B.D.L. 0.30% K23ac 0.71% 1.45% 25 Table S4 Wild type Suz12-/- Wild type Suz12-/- Wild type Suz12-/- K4me1K27me2K36me2 Histone code 1.30% B.D.L. R17me1K27me2K36me2 Histone code 0.16% B.D.L. K9me1K14me2 B.D.L. 0.34% K9me1K14me1K27me3K36me2 1.52% B.D.L. K9me2K23acK27acK36me1 0.15% B.D.L. K9me2K18acK27me1K36me1 B.D.L. 0.82% K9me1K14me1K27me2K36me2 8.54% B.D.L. K23acK36me1 0.15% 0.16% K23me2 B.D.L. 0.76% K9me1K27me2K36me2 11.24% 0.90% K23ac 0.25% 1.46% R40me1R42me2 B.D.L. 0.34% K14me1K27me2K36me2 2.45% B.D.L. K9me1K14me1K18me1K23acK27me2K36me2 0.15% B.D.L. R8me2K18acK27me2K36me2 B.D.L. 0.33% K27me2K36me2 10.25% 0.75% K9me3K14acK27me2K36me2 0.27% 0.18% K23acR42me1 B.D.L. 0.33% K9me1R17me1R26me1K27me2K36me2 0.80% B.D.L. K14acK18me1K23acK27me3 0.14% B.D.L. K37me3 B.D.L. 0.33% K27me3K36me1 2.78% B.D.L. K9me2K23acK27acR49me2 0.13% B.D.L. K9me2K23acK36me1 B.D.L. 1.21% K9me1K23acK27me2K36me2 5.81% B.D.L. K9me1K14acK27me3 0.13% B.D.L. K23acK36me2 B.D.L. 0.52% K27me2K36me1 5.66% B.D.L. K14acK23me3 0.12% 0.35% K9me2K27me1 B.D.L. 0.52% K9me1K18acK23acK27me2K36me2 0.67% B.D.L. K23acK27me1 0.30% 0.12% K18ac B.D.L. 0.62% K9me3K27me2K36me2 7.00% 1.99% K27me3R49me1 0.11% B.D.L. K18me2 B.D.L. 1.23% K18acK27me2K36me2 0.69% B.D.L. K27me2K36me1K37me1 0.23% B.D.L. K9me2K14acR49me2 B.D.L. 0.29% K9me2K27me3 1.23% 0.11% K9me2K23acK27acR49me1 0.10% B.D.L. K9me1K14me1K18acK27me2K36me2 B.D.L. 0.29% K9me1K14me1K18me1K36me2 0.62% 0.37% K23acK36me1K37me1 0.10% B.D.L. R8me1K9me2 B.D.L. 0.28% K9me1K27me2K36me3 0.62% B.D.L. K14acK18me2K23acK36me1K37me1 0.09% B.D.L. K4me1K9me3K36me2 B.D.L. 0.28% K27me3 1.09% 0.55% R26me1K36me2 0.08% B.D.L. K9me2K27me1R40me2 B.D.L. 0.46% K9me1K14me1K36me2 0.61% 9.35% K23acK37me2 0.08% 0.25% R42me2R49me2 B.D.L. 0.27% K9me2K27me3R49me2 0.57% B.D.L. K9me2R26me1K27me1K36me1 0.12% 0.30% K14me1K23acK27me2 B.D.L. 0.27% K9me1K14me1K23acK27me2K36me2 2.06% B.D.L. K27me1K36me1 0.13% B.D.L. K9me1K14me1K23acK27acK36me2 B.D.L. 0.26% K9me1K14me1K23acK36me3 0.53% 0.04% K27me2K37me1 0.07% B.D.L. K4me1K23acK36me2 B.D.L. 0.46% K9me2K23acK27ac 0.50% B.D.L. K9me3K23me1K27me2K36me2 0.06% B.D.L. K9me2K23ac B.D.L. 0.26% K9me1K14me1K23acK36me2 0.49% 2.73% K9me3K27me2K36me1K37me1 0.05% B.D.L. K4me2K23acK27me1K37me2 B.D.L. 0.25% K27me2K36me3 0.47% B.D.L. K14me2K23acK27ac 0.05% B.D.L. K27me1R42me2 B.D.L. 0.24% K27me3K36me3 0.47% B.D.L. K36me2 0.08% 3.17% K14me2K23acK27me1 B.D.L. 0.24% K27me1K36me2 1.50% B.D.L. K27ac 0.04% B.D.L. K18acK23acK37me1 B.D.L. 0.24% K27me3K36me2 1.84% B.D.L. K18acK27me2 0.04% 0.28% K9me2K14me3K23ac B.D.L. 0.23% R8me1R17me1K23acK27me2K36me2 0.46% B.D.L. K9acR17me2K27me2K36me2 0.04% B.D.L. K9me2R17me2K18ac B.D.L. 0.22% K9me1K23acK36me3 0.67% B.D.L. K9me3 0.04% 1.73% K9me1K14acK23me3 B.D.L. 0.21% R26me1K27me1K36me1 0.44% B.D.L. K23acK27me1K36me1 0.07% B.D.L. K9me2K18ac B.D.L. 0.20% K23acK27me2 1.25% 0.29% K36me1 0.04% 1.69% K9me2K14acK18acK36me1K37me1 B.D.L. 0.20% R26me2K27me2K36me2 0.41% B.D.L. R26me2K36me2 0.03% B.D.L. K9acK14me2K27me1K36me1K37me1 B.D.L. 0.46% K9me1R17me1K27me2K36me2 0.49% B.D.L. R8me1K18acK27me2K36me2 0.03% B.D.L. K9me2K23acK27me1K36me1K37me1 B.D.L. 0.31% K9me2K36me3 1.03% 2.02% R42me1 0.03% B.D.L. K9me3R49me1 B.D.L. 0.18% K9me1K23acK27me3 0.39% 0.12% K9me1K36me2 0.03% 9.53% K14me2 B.D.L. 0.25% R8me1K9me1K27me2K36me2 0.39% 0.36% K14me3 0.01% B.D.L. K9me2K23acK27me1 B.D.L. 0.16% K23acK27me2K36me1 1.96% B.D.L. K9me2K36me1K37me1 B.D.L. 2.94% K4me2K18acK27me1K37me2 B.D.L. 0.16% K23acK27me2K36me2 1.94% B.D.L. R17me2K36me2 B.D.L. 0.75% K9me1 B.D.L. 0.32% K9me2K23acK27me3 0.37% B.D.L. K9me2K23me1R49me2 B.D.L. 0.73% R49me2 B.D.L. 0.15% K9me1R26me1K36me3 0.36% B.D.L. K4me3K9me3K23acK36me2 B.D.L. 0.71% R26me1 B.D.L. 0.15% K36me2R42me2 0.36% B.D.L. R8me2K36me2 B.D.L. 0.63% K9me3K36ac B.D.L. 0.14% K9me3R26me1K27me2K36me2 1.18% B.D.L. K14me1K36me2 B.D.L. 0.95% K18me1K36me2 B.D.L. 0.14% K9me3K27me2K36me1 1.32% 0.20% K9me2K27me1K36me1 B.D.L. 4.54% R17me2 B.D.L. 0.22% R26me1K27me2K36me2 0.34% B.D.L. K36me3 B.D.L. 1.02% K9me2K23acR42me2 B.D.L. 0.13% K27me1K36me3 0.63% B.D.L. K9me2K27me1K36me1K37me1 B.D.L. 0.69% R40me2 B.D.L. 0.13% K9acK14me1K18me1K23acK27me2K36me2 0.32% B.D.L. K9me2K36me1 B.D.L. 1.91% K18acK36me2 B.D.L. 0.12% K23acK27me3 0.50% B.D.L. K9me2K18acK27me1K36me1K37me3 B.D.L. 0.56% R17me2K23acK36me1 B.D.L. 0.12% R17me2K27me2K36me2 0.32% B.D.L. K9me2K27me3K36me1 B.D.L. 0.54% K9me2K18acK36me1 B.D.L. 0.12% R26me2K27me2 0.56% B.D.L. K9me1K23acK27me2 B.D.L. 0.53% R17me1K23ac B.D.L. 0.12% K9me1K14me1K18me1K23me1K27me1K36me2 0.29% B.D.L. K4me1K9me1K36me2 B.D.L. 0.52% R26me2 B.D.L. 0.12% K27me1 1.02% 2.04% K9me2K14acK27me1K36me1 B.D.L. 0.68% K9me2K27me1R49me2 B.D.L. 0.11% K23acK27me2K36me1K37me1 0.36% B.D.L. K9me3K36me2 B.D.L. 2.16% K18me1 B.D.L. 0.21% K18acK23acK27me2 0.44% 0.36% K9me2K14acK36me3K37me3 B.D.L. 0.50% K9me2K36me1R49me2 B.D.L. 0.11% K9acK18me1K23me1K36me2 0.27% B.D.L. K9acK14me1K18me1K23acK36me2 B.D.L. 0.83% K23me3 B.D.L. 0.10% K27me2 2.06% 0.95% K14me2K36me1 B.D.L. 0.48% K18acK27me1 B.D.L. 0.10% K27me2R49me2 0.24% B.D.L. K9me2K23acK36me3 B.D.L. 1.23% K14me1K23acK27me3 B.D.L. 0.09% K9me2K27me3K36me1K37me1 0.24% B.D.L. K9me2K27me1K36me3 B.D.L. 0.78% K23acR26me2 B.D.L. 0.09% K14acK18me1K27me2K36me2 0.23% B.D.L. K9me2K14acK27me1K36me1K37me1 B.D.L. 0.48% K18acR26me2 B.D.L. 0.09% K9me2K14acK27me3 0.22% B.D.L. K9me2K23acK27me1K36me1 B.D.L. 1.36% K4me1K23acK36me1K37me1 B.D.L. 0.08% R8me1K9me1K14me1K27me2K36me2 0.21% 0.21% K9me2 B.D.L. 0.69% K14me1 B.D.L. 0.16% K23acR26me1K27me1K36me1 0.21% B.D.L. K9me2K14acK18ac B.D.L. 0.45% K9me2R26me1K27me1 B.D.L. 0.08% K18acK23acK27me1 0.20% B.D.L. R8me1K9me2K37me1 B.D.L. 0.76% K14me3K27me2K36me2 B.D.L. 0.08% K14me3K18me3K23acK27me2K36me2 0.19% B.D.L. K27me2R42me2 B.D.L. 0.44% K9me2R17me1K36me1K37me1 B.D.L. 0.08% K14me1K23acK27me2K36me2 0.30% B.D.L. K9me1K14me1K18acK23acK36me2 B.D.L. 0.44% K9me2K18acK27me1K36me1K37me1 B.D.L. 0.07% K9me3K14me3K23acK27me2K36me2 0.18% B.D.L. R8me2K18acK36me3 B.D.L. 0.43% R26me1K27me1 B.D.L. 0.07% (unmodified) 1.49% 7.15% K23me1 B.D.L. 0.72% K9me3K14me1 B.D.L. 0.06% K9me1K18acK27me2K36me2 0.34% B.D.L. K9me2K14me1 B.D.L. 0.41% R8me1K9me1K18ac B.D.L. 0.06% K9acK14me3K27me2K36me2 0.24% 0.18% K9me1K14me1K18acK36me2 B.D.L. 0.97% R8me1R17me1K27me1 B.D.L. 0.04% R17me1R26me1K36me2 0.17% B.D.L. K9me2K23acK36me1K37me1 B.D.L. 0.40% K14me2K23acK36me1 B.D.L. 0.04% K9me3K23acK27me2K36me2 0.27% B.D.L. K36me1R42me2 B.D.L. 0.38% K9acK14me2K27me1K36me1 B.D.L. 0.01% K9acK18me1K27me2K36me2 0.16% B.D.L. R8me2K14acK27me2K36me2 B.D.L. 0.38% K9me3K36me1K37me1 B.D.L. 0.01% K36me1K37me2 B.D.L. 0.38% 26 Histone code Table S5 Wild type Suz12-/- t-test Wild type Suz12-/- t-test Wild type Suz12-/- t-test K27me2K36me2 Binary co-existence 70.27% 11.84% 2.64E-11 K27me1K37me3 Binary co-existence 0.16% 0.00% 1.73E-02 K18me3K36me2 0.03% 0.01% 8.76E-02 K14me1K27me2 20.69% 1.81% 1.09E-09 K36me1K37me3 0.16% 0.00% 1.74E-02 K9acK27me1 0.02% 0.30% 8.95E-02 K9me2K27me1 1.74% 16.61% 1.16E-09 K9acK27me2 3.25% 0.25% 1.76E-02 K9acK27me3 0.09% 0.00% 9.02E-02 K27me1K36me1 2.18% 14.65% 1.35E-08 K9me3K37me2 0.00% 0.02% 1.81E-02 R8me1K9ac 0.03% 0.00% 9.21E-02 K9me2K36me1 3.22% 22.11% 4.41E-08 R42me2R49me2 0.18% 0.03% 1.81E-02 R8me1R26me1 0.03% 0.00% 9.21E-02 K27me2K36me1 3.89% 0.34% 8.37E-08 K27me3R40me1 0.23% 0.00% 1.87E-02 K23acK37me2 0.02% 0.00% 9.30E-02 K9me1K27me2 37.27% 10.11% 1.09E-07 K23acK36me3 0.98% 2.24% 1.88E-02 R26me1K37me1 0.14% 0.43% 9.39E-02 K27me1K37me1 1.03% 6.78% 2.50E-07 K9me2K14me1 0.00% 0.08% 1.91E-02 K37me1R42me1 0.00% 0.04% 9.40E-02 K9me2K37me1 1.85% 10.90% 2.14E-06 R26me2K27me1 0.14% 0.00% 2.02E-02 K23me3K27ac 0.29% 0.00% 9.47E-02 R26me1K27me2 1.03% 0.01% 2.75E-06 K14me1K23ac 6.88% 3.63% 2.03E-02 K18acK23me2 0.05% 0.00% 9.54E-02 K36me1K37me1 2.92% 11.58% 4.46E-06 K36me1R40me1 0.00% 0.46% 2.23E-02 R8me1K27me3 0.07% 0.00% 9.77E-02 R26me1K36me2 1.13% 0.05% 6.80E-06 K9me1K18me1 0.04% 0.24% 2.24E-02 R8me2K27me2 0.75% 0.46% 9.83E-02 K9me2K23ac 0.80% 9.47% 1.44E-05 K14me1K23me2 0.03% 0.00% 2.46E-02 K9me1K18ac 3.15% 2.19% 9.86E-02 K9me2R40me2 0.34% 4.43% 1.57E-05 R8me1K36me1 0.07% 0.35% 2.57E-02 K27me1R40me1 0.03% 0.58% 1.04E-01 K4me1K36me2 1.38% 4.46% 1.82E-04 K18me1K23me2 0.25% 0.00% 2.71E-02 K23me1K36me1 0.03% 0.18% 1.05E-01 K14me1K27me3 0.24% 0.00% 2.11E-04 K27me2R40me1 0.04% 0.00% 2.79E-02 K23acK37me3 0.24% 0.10% 1.05E-01 K9me2K18ac 0.47% 4.42% 2.19E-04 K23me3K36ac 0.00% 0.09% 2.86E-02 K27acR40me2 0.02% 0.00% 1.06E-01 K23acK27me2 23.19% 1.51% 2.52E-04 K18me2K23me2 0.04% 0.00% 3.01E-02 K14acK23me3 1.06% 0.53% 1.09E-01 K9me3K27me2 10.81% 2.82% 2.81E-04 K9me1K14me1 17.87% 14.08% 3.08E-02 K9acK18me2 0.01% 0.00% 1.10E-01 K9me2K36me3 0.94% 7.12% 2.85E-04 K9me2K23me1 0.10% 0.36% 3.21E-02 R8me1K18ac 0.16% 0.05% 1.12E-01 K27me2K36me3 0.37% 0.00% 3.69E-04 K14me3K27me2 0.17% 0.01% 3.22E-02 K18acK37me3 0.08% 0.00% 1.12E-01 K14me1K36me2 21.22% 14.74% 4.01E-04 K4me1K36me3 0.00% 0.40% 3.26E-02 K9acK14me1 2.39% 0.95% 1.13E-01 K9me2K14ac 0.50% 9.19% 4.06E-04 K9acK23me2 0.18% 0.00% 3.39E-02 K27me2K37me3 0.05% 0.00% 1.13E-01 K9me2R42me2 0.18% 1.13% 4.66E-04 K9acR26me1 0.06% 0.00% 3.58E-02 K9me3K18me2 0.02% 0.00% 1.15E-01 K18acK27me2 8.76% 1.25% 5.11E-04 K23me2K27ac 0.19% 0.00% 3.64E-02 K9acK36me3 0.00% 0.04% 1.17E-01 K9me1K36me2 37.38% 24.94% 5.43E-04 R8me1K27me1 0.07% 0.32% 3.66E-02 K18me2K27me2 0.02% 0.00% 1.17E-01 K18acK36me2 7.06% 1.69% 5.73E-04 K18acK36me3 0.15% 0.52% 3.71E-02 K18me2K36me2 0.02% 0.00% 1.17E-01 K14acK37me1 0.64% 2.64% 6.01E-04 K9me3K36ac 0.01% 0.10% 3.72E-02 R8me2K14ac 0.34% 0.09% 1.17E-01 K14acK36me1 1.01% 5.19% 6.97E-04 K18acK23me3 0.03% 0.00% 3.79E-02 K27me1R42me1 0.01% 0.31% 1.19E-01 K27me1R40me2 0.06% 1.34% 8.28E-04 K23me3K36me2 0.38% 0.02% 3.80E-02 R26me1R40me1 0.02% 0.30% 1.20E-01 K9me3K23ac 1.37% 0.13% 8.89E-04 K18me2K37me1 0.04% 0.00% 3.90E-02 K23acR40me1 0.00% 0.06% 1.20E-01 K14acK27me1 1.27% 4.00% 9.15E-04 K4me1K23ac 1.08% 1.74% 3.90E-02 K18me2K36me3 0.03% 0.00% 1.20E-01 R17me1K27me2 1.19% 0.03% 1.05E-03 K9me1R17me2 0.00% 0.17% 4.05E-02 K18me2K23me1 0.04% 0.00% 1.20E-01 K27me3K37me2 0.02% 0.00% 1.16E-03 K27me2R49me2 0.04% 0.00% 4.07E-02 K18me2K27ac 0.04% 0.00% 1.20E-01 K27me3K36me1 2.60% 0.08% 1.26E-03 K23me1K27me2 0.03% 0.00% 4.15E-02 K18me2K27me3 0.07% 0.00% 1.20E-01 K9me3K36me2 10.70% 4.15% 1.28E-03 K27me2R40me2 0.08% 0.00% 4.23E-02 R8me2K36me2 0.75% 0.49% 1.21E-01 K27me3K36me2 1.34% 0.00% 1.35E-03 K9me2K36ac 0.13% 0.55% 4.26E-02 K4me1R8me2 0.01% 0.06% 1.21E-01 K23acK27me1 1.79% 4.49% 1.57E-03 K9me3K36me1 0.19% 0.55% 4.27E-02 R17me1K23ac 0.13% 0.32% 1.22E-01 K23acK36me2 19.02% 6.72% 1.64E-03 K14me2R42me2 0.04% 0.00% 4.29E-02 K9me2R40me1 0.24% 0.76% 1.22E-01 K23acK37me1 1.00% 2.74% 1.67E-03 K9me1R17me1 0.73% 0.33% 4.42E-02 K9me1K36me3 0.65% 0.19% 1.23E-01 K23acR42me2 0.19% 0.48% 1.73E-03 R8me1R17me1 0.50% 0.18% 4.44E-02 R17me1K23me2 0.06% 0.00% 1.24E-01 K9me3K14ac 3.13% 1.05% 1.79E-03 K9me3K27me1 0.03% 0.29% 4.49E-02 K27me3R49me2 0.06% 0.00% 1.24E-01 K4me1K18ac 0.26% 1.34% 1.97E-03 R17me2K23ac 0.01% 0.06% 4.55E-02 K14me1R42me1 0.00% 0.01% 1.25E-01 K4me1K9me1 1.26% 3.61% 2.01E-03 K18me2K27me1 0.06% 0.00% 4.55E-02 K4me1K27me1 0.10% 0.40% 1.26E-01 K4me1K14ac 0.62% 2.93% 2.03E-03 K14acK23me2 0.73% 0.15% 4.70E-02 R17me1R26me1 0.20% 0.00% 1.26E-01 K27me3K37me1 1.20% 0.07% 2.13E-03 K18me2K23ac 0.21% 0.92% 4.80E-02 K27me1R49me2 0.03% 0.17% 1.26E-01 K9me1K27me3 0.74% 0.00% 2.13E-03 R8me1K23me2 0.13% 0.00% 4.84E-02 K23me3K37me1 0.17% 0.00% 1.27E-01 K9me3K18ac 1.58% 0.10% 2.20E-03 K9me1K18me2 0.00% 0.10% 4.84E-02 K9me3K27ac 0.05% 0.00% 1.28E-01 K14me1K18ac 1.11% 0.52% 2.21E-03 K27me2R42me1 0.03% 0.00% 5.05E-02 K4me1K9me2 0.18% 0.44% 1.29E-01 K14acK27me2 12.63% 3.24% 2.24E-03 K18acK23ac 2.91% 1.58% 5.17E-02 K9acR17me1 0.16% 0.01% 1.31E-01 K9me1K23ac 9.99% 4.53% 2.56E-03 R26me2K36me3 0.03% 0.00% 5.37E-02 K18acR40me2 0.08% 0.55% 1.32E-01 K27me1K36me2 1.59% 0.35% 2.64E-03 K14acK36me3 0.41% 1.23% 5.38E-02 K14me3K27me1 0.00% 0.11% 1.32E-01 K9me1R40me2 0.00% 0.40% 2.79E-03 K23me1K36me3 0.11% 0.01% 5.59E-02 K14me3R40me1 0.00% 0.00% 1.32E-01 K18acK37me1 0.19% 1.27% 2.89E-03 K9me2K27me3 2.81% 1.29% 5.62E-02 K9acK23ac 1.84% 0.92% 1.34E-01 K27me3R40me2 0.19% 0.00% 3.60E-03 K18me1K36me3 0.13% 0.01% 5.97E-02 K9acK23me3 0.14% 0.00% 1.36E-01 K9me2R26me1 0.06% 1.00% 3.72E-03 K9me1K14me2 0.01% 0.49% 6.26E-02 K23me3K36me1 0.28% 0.07% 1.36E-01 K14me2K27ac 0.05% 0.00% 4.06E-03 K9me1K23me2 0.32% 0.13% 6.27E-02 K27acK37me1 0.11% 0.04% 1.36E-01 K14acK36me2 9.96% 3.50% 4.13E-03 K23me1K37me1 0.00% 0.18% 6.38E-02 K9me3K37me1 0.23% 0.44% 1.37E-01 K18acK27me1 0.90% 2.54% 5.16E-03 K14acK18me2 0.26% 0.92% 6.41E-02 R26me1R42me1 0.01% 0.21% 1.37E-01 K18acK36me1 0.54% 2.56% 5.26E-03 K27me2K36ac 0.04% 0.01% 6.57E-02 K14acR26me2 0.04% 0.01% 1.38E-01 K27me2K37me1 0.69% 0.12% 6.67E-03 R26me2K37me1 0.06% 0.00% 6.64E-02 K36me2K37me1 0.08% 0.01% 1.40E-01 R17me1K36me2 1.27% 0.23% 6.69E-03 K9me2R49me2 0.37% 1.03% 6.76E-02 K18me2K36ac 0.02% 0.00% 1.40E-01 K23me1K36ac 0.00% 0.05% 7.24E-03 K14acR49me2 0.04% 0.36% 6.84E-02 K23acR42me1 0.01% 0.06% 1.42E-01 K14me1K27ac 0.00% 0.16% 7.95E-03 K4me1K14me1 0.19% 0.44% 6.86E-02 R17me1K23me1 0.00% 0.07% 1.43E-01 K14acR40me2 0.01% 1.42% 8.02E-03 K18me1K36me2 2.69% 1.22% 7.09E-02 K27me2R42me2 0.01% 0.00% 1.44E-01 K18me1K27me2 3.14% 0.00% 8.15E-03 K9acK36me2 3.34% 1.23% 7.10E-02 K9acK18me1 2.08% 1.06% 1.44E-01 K23acR26me1 0.98% 0.10% 8.33E-03 K14me1K36ac 0.00% 0.05% 7.28E-02 R17me1K36me1 0.12% 0.28% 1.45E-01 K4me1K27me3 0.55% 0.02% 8.46E-03 R17me1K18me1 0.00% 0.17% 7.39E-02 K9acR42me2 0.02% 0.00% 1.45E-01 K23acR40me2 0.04% 0.97% 8.79E-03 K27me3R42me1 0.13% 0.00% 7.74E-02 K18acR26me2 0.10% 0.02% 1.48E-01 K23acK36me1 3.34% 6.65% 9.06E-03 K23me2K27me3 0.06% 0.00% 7.85E-02 K9me2K18me1 0.07% 0.34% 1.49E-01 K18me2K36me1 0.10% 0.00% 9.73E-03 R26me2K36me2 0.17% 0.02% 7.86E-02 K9me1R42me2 0.11% 0.00% 1.49E-01 K23me2R26me1 0.08% 0.00% 9.95E-03 R17me1R26me2 0.00% 0.03% 7.87E-02 R26me1R42me2 0.11% 0.00% 1.49E-01 R8me1K14me1 0.54% 0.03% 1.06E-02 K9me1K27ac 0.03% 0.11% 8.02E-02 K14me1K23me3 0.00% 0.03% 1.50E-01 R26me2K36me1 0.15% 0.01% 1.18E-02 K9me1R26me2 0.00% 0.01% 8.11E-02 K27acR42me1 0.01% 0.00% 1.50E-01 K9me2R17me1 0.00% 0.24% 1.27E-02 R8me2K18ac 0.31% 0.05% 8.36E-02 K4me1K14me3 0.00% 0.00% 1.51E-01 K23me1K36me2 0.78% 0.16% 1.33E-02 K14me3R42me1 0.00% 0.00% 8.40E-02 R8me2K14me3 0.00% 0.00% 1.51E-01 K23me2K36me2 1.03% 0.15% 1.34E-02 K23me3K27me3 0.50% 0.09% 8.53E-02 R8me1K14me3 0.00% 0.00% 1.51E-01 K23acK27me3 0.92% 0.06% 1.44E-02 K14me2K36me1 0.00% 0.21% 8.56E-02 K9me1K14me3 0.00% 0.00% 1.51E-01 K23me2K27me2 1.03% 0.18% 1.67E-02 K36me1R42me1 0.00% 0.11% 8.59E-02 K14me3R17me1 0.00% 0.00% 1.51E-01 K23me3K27me2 0.51% 0.00% 1.68E-02 R17me2K18me1 0.00% 0.03% 8.74E-02 K14me3R17me2 0.00% 0.00% 1.51E-01 27 Binary co-existence Table S5 - continues Wild type Suz12-/- t-test Wild type Suz12-/- t-test Wild type Suz12-/- t-test K14me3K18me1 Binary co-existence 0.00% 0.00% 1.51E-01 K9me3K14me2 Binary co-existence 0.00% 0.00% 1.90E-01 K36me3K37me3 0.00% 0.00% 2.90E-01 K14me3K23me1 0.00% 0.00% 1.51E-01 K14me2R17me2 0.00% 0.00% 1.90E-01 K37me3R40me2 0.00% 0.00% 2.90E-01 K14me3K23me2 0.00% 0.00% 1.51E-01 K14me2K18me1 0.00% 0.00% 1.90E-01 K37me3R49me2 0.00% 0.00% 2.90E-01 K14me3R26me2 0.00% 0.00% 1.51E-01 K14me2K23me1 0.00% 0.00% 1.90E-01 R17me2K18ac 0.05% 0.08% 2.90E-01 K14me3R26me1 0.00% 0.00% 1.51E-01 K14me2K23me2 0.00% 0.00% 1.90E-01 K18acR49me2 0.04% 0.07% 2.93E-01 K14me3K27me3 0.00% 0.00% 1.51E-01 K14me2R26me1 0.00% 0.00% 1.90E-01 K18acK23me1 0.04% 0.08% 2.95E-01 K14me3K27ac 0.00% 0.00% 1.51E-01 K14me2R26me2 0.00% 0.00% 1.90E-01 K9me2K14me2 0.00% 0.01% 2.96E-01 K14me3K36me3 0.00% 0.00% 1.51E-01 K14me2K27me3 0.00% 0.00% 1.90E-01 K14me2K36me3 0.00% 0.03% 2.99E-01 K14me3R40me2 0.00% 0.00% 1.51E-01 K14me2K27me2 0.00% 0.00% 1.90E-01 K4me1K18me3 0.00% 0.00% 2.99E-01 K14me3R49me2 0.00% 0.00% 1.51E-01 K14me2K36me2 0.00% 0.00% 1.90E-01 R8me1K18me3 0.00% 0.00% 2.99E-01 R26me1K27me3 0.10% 0.00% 1.51E-01 K14me2K37me1 0.00% 0.00% 1.90E-01 R8me2K18me3 0.00% 0.00% 2.99E-01 K14me3K36me1 0.01% 0.11% 1.52E-01 K14me2R40me2 0.00% 0.00% 1.90E-01 K9me1K18me3 0.00% 0.00% 2.99E-01 K4me1K9ac 0.12% 0.00% 1.54E-01 K14me2R42me1 0.00% 0.00% 1.90E-01 K9me2K18me3 0.00% 0.00% 2.99E-01 R26me2K27ac 0.00% 0.00% 1.54E-01 K14me2R49me2 0.00% 0.00% 1.90E-01 K14acK18me3 0.00% 0.00% 2.99E-01 R17me1K36me3 0.00% 0.05% 1.55E-01 K9acR49me2 0.00% 0.00% 1.92E-01 R17me1K18me3 0.00% 0.00% 2.99E-01 K9me2R42me1 0.14% 0.47% 1.56E-01 K14me1K18me1 2.16% 1.30% 1.93E-01 R17me2K18me3 0.00% 0.00% 2.99E-01 R17me1K27ac 0.00% 0.06% 1.60E-01 K23me3R26me1 0.09% 0.00% 1.94E-01 K18me3K23ac 0.00% 0.00% 2.99E-01 K14me1R40me1 0.00% 0.04% 1.60E-01 K14acR42me1 0.00% 0.03% 1.94E-01 K18me3K23me1 0.00% 0.00% 2.99E-01 K14me3K23ac 0.06% 0.17% 1.62E-01 K9me1R26me1 0.36% 0.10% 1.97E-01 K18me3K23me2 0.00% 0.00% 2.99E-01 K4me1K27me2 1.41% 1.92% 1.63E-01 K27acK36me3 0.06% 0.01% 1.99E-01 K18me3R26me1 0.00% 0.00% 2.99E-01 K9me3R26me1 0.03% 0.01% 1.63E-01 K14me2R17me1 0.00% 0.06% 2.01E-01 K18me3R26me2 0.00% 0.00% 2.99E-01 K14me1R26me1 0.05% 0.02% 1.63E-01 K9me1K36me1 0.31% 0.19% 2.02E-01 K18me3K27ac 0.00% 0.00% 2.99E-01 K14me1K36me3 0.00% 0.05% 1.64E-01 K14me3R42me2 0.00% 0.00% 2.06E-01 K18me3K27me1 0.00% 0.00% 2.99E-01 K9me2K14me3 0.00% 0.02% 1.64E-01 R8me1K36me3 0.01% 0.05% 2.06E-01 K18me3K27me3 0.00% 0.00% 2.99E-01 K14me2K18me3 0.00% 0.00% 1.65E-01 K9me3K23me2 0.34% 0.17% 2.08E-01 K18me3K36me1 0.00% 0.00% 2.99E-01 K4me1K9me3 0.00% 0.01% 1.65E-01 R17me1K27me3 0.05% 0.01% 2.10E-01 K18me3K36me3 0.00% 0.00% 2.99E-01 K36me3K37me1 0.00% 0.01% 1.65E-01 R26me2R40me2 0.12% 0.05% 2.11E-01 K18me3K37me1 0.00% 0.00% 2.99E-01 K27me1K36ac 0.18% 0.33% 1.66E-01 K14me2K27me1 0.00% 0.11% 2.13E-01 K18me3R40me2 0.00% 0.00% 2.99E-01 R17me2K27ac 0.00% 0.01% 1.67E-01 K9acK14me2 0.04% 0.17% 2.13E-01 K18me3R42me1 0.00% 0.00% 2.99E-01 K14me3K18ac 0.01% 0.12% 1.67E-01 K14acR26me1 0.33% 0.18% 2.13E-01 K18me3R49me2 0.00% 0.00% 2.99E-01 K27acR49me2 0.13% 0.03% 1.67E-01 R17me2K36me2 0.69% 0.47% 2.17E-01 K4me1R8me1 0.07% 0.13% 2.99E-01 K14acR42me2 0.05% 0.15% 1.67E-01 K37me1R40me1 0.00% 0.01% 2.20E-01 K9me1K23me1 0.00% 0.01% 3.01E-01 K14me3K37me1 0.00% 0.02% 1.68E-01 K14me2K23me3 0.00% 0.00% 2.21E-01 K36me2K37me2 0.00% 0.01% 3.06E-01 K23me1K27me1 0.61% 0.41% 1.68E-01 K27me1K36me3 0.72% 0.50% 2.23E-01 K27acK36me1 0.14% 0.18% 3.07E-01 R17me2K27me2 0.69% 0.42% 1.68E-01 R26me1K27me1 0.68% 0.90% 2.29E-01 K4me1K23me3 0.00% 0.00% 3.08E-01 K9me3K23me1 0.00% 0.01% 1.68E-01 K9acR17me2 0.43% 0.24% 2.33E-01 R8me1K23me3 0.00% 0.00% 3.08E-01 K9acK18me3 0.00% 0.01% 1.69E-01 K18me1K23ac 2.85% 1.98% 2.34E-01 R8me2K23me3 0.00% 0.00% 3.08E-01 K18me1K27me1 0.10% 0.21% 1.69E-01 K18me1K23me1 0.44% 0.29% 2.36E-01 K9me3K23me3 0.00% 0.00% 3.08E-01 K14me1R17me2 0.00% 0.02% 1.69E-01 K18acR26me1 0.12% 0.24% 2.39E-01 R17me1K23me3 0.00% 0.00% 3.08E-01 K14acK36ac 0.01% 0.00% 1.69E-01 K4me1K36me1 0.60% 0.40% 2.42E-01 R17me2K23me3 0.00% 0.00% 3.08E-01 R8me1K9me2 0.00% 0.07% 1.70E-01 K23acK36ac 0.20% 0.12% 2.43E-01 K18me1K23me3 0.00% 0.00% 3.08E-01 K9acR26me2 0.01% 0.00% 1.70E-01 K14me2K18ac 0.04% 0.11% 2.44E-01 K23me3R26me2 0.00% 0.00% 3.08E-01 K4me1K37me1 0.68% 0.42% 1.70E-01 K14acK18ac 7.41% 5.94% 2.45E-01 K23me3K36me3 0.00% 0.00% 3.08E-01 R8me2R26me1 0.04% 0.00% 1.70E-01 K27me3K36ac 0.02% 0.01% 2.46E-01 K23me3R40me2 0.00% 0.00% 3.08E-01 R8me2K23me2 0.16% 0.00% 1.70E-01 K23me3R42me2 0.00% 0.00% 2.46E-01 K23me3R49me2 0.00% 0.00% 3.08E-01 K9acK37me1 0.12% 0.00% 1.70E-01 K14acR17me2 0.17% 0.07% 2.47E-01 K23me2R26me2 0.04% 0.02% 3.09E-01 K23me1K27me3 0.00% 0.02% 1.71E-01 R17me1K37me1 0.08% 0.16% 2.48E-01 K36acK37me2 0.00% 0.00% 3.11E-01 K23me2K27me1 0.01% 0.00% 1.71E-01 R17me1K18ac 0.16% 0.07% 2.50E-01 K23me3K27me1 0.21% 0.14% 3.13E-01 R8me1K18me1 0.00% 0.02% 1.71E-01 K18me2R42me2 0.00% 0.00% 2.51E-01 K23me3R40me1 0.00% 0.00% 3.15E-01 R8me1K27ac 0.00% 0.02% 1.71E-01 K14me1R17me1 0.12% 0.19% 2.54E-01 K9me1K14ac 3.94% 3.32% 3.18E-01 K4me1K36ac 0.02% 0.00% 1.71E-01 R8me1K23ac 0.22% 0.32% 2.54E-01 K36acR42me2 0.00% 0.00% 3.23E-01 R8me1K36ac 0.02% 0.00% 1.71E-01 K14me2K23ac 0.04% 0.10% 2.59E-01 R26me1K36me3 0.09% 0.14% 3.24E-01 K37me1R49me2 0.01% 0.00% 1.71E-01 K27me1R42me2 0.01% 0.02% 2.78E-01 K9me1R42me1 0.04% 0.06% 3.25E-01 K18acK36ac 0.03% 0.00% 1.71E-01 R8me1K9me1 4.53% 5.10% 2.79E-01 K4me1K37me2 0.00% 0.00% 3.25E-01 K9me3K14me1 0.01% 0.00% 1.72E-01 K4me1R17me1 0.13% 0.07% 2.80E-01 R8me1K37me2 0.00% 0.00% 3.25E-01 R8me2K36me1 0.00% 0.04% 1.72E-01 K9acK14me3 0.05% 0.12% 2.82E-01 R8me2K37me2 0.00% 0.00% 3.25E-01 K18me2K23me3 0.00% 0.00% 1.72E-01 K23me3K37me2 0.00% 0.01% 2.82E-01 K9acK37me2 0.00% 0.00% 3.25E-01 K9me1K37me1 0.32% 0.19% 1.73E-01 R26me1K36ac 0.05% 0.02% 2.88E-01 K9me1K37me2 0.00% 0.00% 3.25E-01 K18me1R26me2 0.00% 0.02% 1.73E-01 K27acR42me2 0.02% 0.01% 2.88E-01 K9me2K37me2 0.00% 0.00% 3.25E-01 R17me1K36ac 0.00% 0.03% 1.73E-01 K14me3K36ac 0.00% 0.00% 2.88E-01 K14acK37me2 0.00% 0.00% 3.25E-01 K18me1K36ac 0.00% 0.01% 1.74E-01 K4me1K37me3 0.00% 0.00% 2.90E-01 K14me1K37me2 0.00% 0.00% 3.25E-01 K18me1R26me1 0.02% 0.00% 1.75E-01 R8me1K37me3 0.00% 0.00% 2.90E-01 R17me1K37me2 0.00% 0.00% 3.25E-01 K18me3K36ac 0.00% 0.01% 1.75E-01 R8me2K37me3 0.00% 0.00% 2.90E-01 R17me2K37me2 0.00% 0.00% 3.25E-01 K23me1R49me2 0.00% 0.01% 1.77E-01 K9acK37me3 0.00% 0.00% 2.90E-01 K18acK37me2 0.00% 0.00% 3.25E-01 K9me1K27me1 0.10% 0.19% 1.79E-01 K9me1K37me3 0.00% 0.00% 2.90E-01 K18me1K37me2 0.00% 0.00% 3.25E-01 K9me3R49me2 0.00% 0.01% 1.79E-01 K9me3K37me3 0.00% 0.00% 2.90E-01 K18me2K37me2 0.00% 0.00% 3.25E-01 K18me3K37me3 0.00% 0.00% 1.81E-01 K14me3K18me2 0.00% 0.00% 2.90E-01 K23me1K37me2 0.00% 0.00% 3.25E-01 K37me3R40me1 0.00% 0.00% 1.81E-01 K14me1K37me3 0.00% 0.00% 2.90E-01 K23me2K37me2 0.00% 0.00% 3.25E-01 K37me3R42me1 0.00% 0.00% 1.81E-01 K14me3K37me3 0.00% 0.00% 2.90E-01 R26me1K37me2 0.00% 0.00% 3.25E-01 K9me3K18me3 0.01% 0.00% 1.84E-01 R17me2K37me3 0.00% 0.00% 2.90E-01 R26me2K37me2 0.00% 0.00% 3.25E-01 K14me1K18me3 0.01% 0.00% 1.84E-01 R17me1K37me3 0.00% 0.00% 2.90E-01 K27acK37me2 0.00% 0.00% 3.25E-01 K18me3K27me2 0.01% 0.00% 1.84E-01 K18me2K37me3 0.00% 0.00% 2.90E-01 K27me1K37me2 0.00% 0.00% 3.25E-01 R26me1R40me2 0.00% 0.06% 1.84E-01 K18me1K37me3 0.00% 0.00% 2.90E-01 K27me2K37me2 0.00% 0.00% 3.25E-01 K9me1K36ac 0.09% 0.04% 1.85E-01 K23me2K37me3 0.00% 0.00% 2.90E-01 K36me1K37me2 0.00% 0.00% 3.25E-01 R17me1K27me1 0.12% 0.03% 1.89E-01 K23me1K37me3 0.00% 0.00% 2.90E-01 K36me3K37me2 0.00% 0.00% 3.25E-01 K9me1K23me3 0.02% 0.00% 1.90E-01 R26me1K37me3 0.00% 0.00% 2.90E-01 K37me2R40me1 0.00% 0.00% 3.25E-01 K14me3K18me3 0.00% 0.01% 1.90E-01 R26me2K37me3 0.00% 0.00% 2.90E-01 K37me2R40me2 0.00% 0.00% 3.25E-01 K4me1K14me2 0.00% 0.00% 1.90E-01 K27me3K37me3 0.00% 0.00% 2.90E-01 K37me2R42me1 0.00% 0.00% 3.25E-01 R8me2K14me2 0.00% 0.00% 1.90E-01 K27acK37me3 0.00% 0.00% 2.90E-01 K37me2R42me2 0.00% 0.00% 3.25E-01 R8me1K14me2 0.00% 0.00% 1.90E-01 K36me2K37me3 0.00% 0.00% 2.90E-01 K37me2R49me2 0.00% 0.00% 3.25E-01 28 Binary co-existence Table S5 - continues Wild type Suz12-/- t-test Wild type Suz12-/- t-test Wild type Suz12-/- t-test K14me3K23me3 Binary co-existence 0.00% 0.00% 3.29E-01 R8me2R17me2 Binary co-existence 0.00% 0.00% 4.34E-01 K9acK18ac 0.24% 0.22% 4.53E-01 K9me1R40me1 0.04% 0.06% 3.30E-01 R8me2K18me1 0.00% 0.00% 4.34E-01 R8me1K14ac 0.09% 0.08% 4.54E-01 K18acR42me2 0.06% 0.10% 3.31E-01 R8me2K23me1 0.00% 0.00% 4.34E-01 K27me3K36me3 0.11% 0.12% 4.54E-01 K9acK23me1 0.12% 0.17% 3.34E-01 R8me1R26me2 0.00% 0.00% 4.34E-01 K18acK27ac 0.07% 0.06% 4.59E-01 K14acK27ac 0.34% 0.23% 3.35E-01 R8me2R26me2 0.00% 0.00% 4.34E-01 K4me1R40me1 0.00% 0.00% 4.62E-01 K9me3R26me2 0.06% 0.04% 3.45E-01 R8me2K27ac 0.00% 0.00% 4.34E-01 R8me1R40me1 0.00% 0.00% 4.62E-01 K18acK27me3 0.44% 0.67% 3.47E-01 R8me2K27me1 0.00% 0.00% 4.34E-01 R8me2R40me1 0.00% 0.00% 4.62E-01 K9me3K14me3 0.09% 0.13% 3.48E-01 R8me2K27me3 0.00% 0.00% 4.34E-01 K9acR40me1 0.00% 0.00% 4.62E-01 K9acK27ac 0.03% 0.05% 3.52E-01 R8me2K36me3 0.00% 0.00% 4.34E-01 K9me3R40me1 0.00% 0.00% 4.62E-01 K36acK37me3 0.00% 0.00% 3.55E-01 R8me2K37me1 0.00% 0.00% 4.34E-01 K14acR40me1 0.00% 0.00% 4.62E-01 K14acK18me1 1.43% 1.20% 3.59E-01 R8me1R40me2 0.00% 0.00% 4.34E-01 R17me1R40me1 0.00% 0.00% 4.62E-01 K9me2K23me3 0.45% 0.36% 3.60E-01 R8me2R40me2 0.00% 0.00% 4.34E-01 R17me2R40me1 0.00% 0.00% 4.62E-01 R26me1K36me1 0.69% 0.78% 3.64E-01 R8me1R49me2 0.00% 0.00% 4.34E-01 K18acR40me1 0.00% 0.00% 4.62E-01 R8me1K36me2 4.86% 5.22% 3.64E-01 R8me2R49me2 0.00% 0.00% 4.34E-01 K18me1R40me1 0.00% 0.00% 4.62E-01 K4me1R42me1 0.00% 0.00% 3.65E-01 K9me3R17me1 0.00% 0.00% 4.34E-01 K23me1R40me1 0.00% 0.00% 4.62E-01 R8me1R42me1 0.00% 0.00% 3.65E-01 K9me2R17me2 0.00% 0.00% 4.34E-01 K23me2R40me1 0.00% 0.00% 4.62E-01 R8me2R42me1 0.00% 0.00% 3.65E-01 K9me3R17me2 0.00% 0.00% 4.34E-01 R26me2R40me1 0.00% 0.00% 4.62E-01 K9acR42me1 0.00% 0.00% 3.65E-01 K9me3K18me1 0.00% 0.00% 4.34E-01 K27acR40me1 0.00% 0.00% 4.62E-01 K9me3R42me1 0.00% 0.00% 3.65E-01 K9me2K23me2 0.00% 0.00% 4.34E-01 K36me2R40me1 0.00% 0.00% 4.62E-01 R17me1R42me1 0.00% 0.00% 3.65E-01 K9me2K27me2 0.00% 0.00% 4.34E-01 K36me3R40me1 0.00% 0.00% 4.62E-01 R17me2R42me1 0.00% 0.00% 3.65E-01 K9me3K27me3 0.00% 0.00% 4.34E-01 R40me1R49me2 0.00% 0.00% 4.62E-01 K18acR42me1 0.00% 0.00% 3.65E-01 K9me2K36me2 0.00% 0.00% 4.34E-01 K23acR26me2 0.13% 0.12% 4.66E-01 K18me1R42me1 0.00% 0.00% 3.65E-01 K9me3K36me3 0.00% 0.00% 4.34E-01 K14acK27me3 0.91% 0.87% 4.68E-01 K23me1R42me1 0.00% 0.00% 3.65E-01 K9acR40me2 0.00% 0.00% 4.34E-01 K4me1K27ac 0.01% 0.01% 4.69E-01 K23me2R42me1 0.00% 0.00% 3.65E-01 K9me3R40me2 0.00% 0.00% 4.34E-01 K9me2K27ac 0.51% 0.53% 4.70E-01 R26me2R42me1 0.00% 0.00% 3.65E-01 K9me1R49me2 0.00% 0.00% 4.34E-01 K18me3K23me3 0.00% 0.00% 4.70E-01 K36me2R42me1 0.00% 0.00% 3.65E-01 K14me1R26me2 0.00% 0.00% 4.34E-01 K23me2K36me1 0.01% 0.01% 4.74E-01 K36me3R42me1 0.00% 0.00% 3.65E-01 K14me1K27me1 0.00% 0.00% 4.34E-01 K14acK37me3 0.08% 0.09% 4.75E-01 R40me2R42me1 0.00% 0.00% 3.65E-01 K14me1K36me1 0.00% 0.00% 4.34E-01 K36acR40me1 0.00% 0.00% 4.79E-01 R42me1R49me2 0.00% 0.00% 3.65E-01 K14me1K37me1 0.00% 0.00% 4.34E-01 K36acR42me1 0.00% 0.00% 4.79E-01 R8me2K23ac 0.17% 0.11% 3.66E-01 K14me1R40me2 0.00% 0.00% 4.34E-01 K9acK14ac 0.07% 0.07% 4.79E-01 K4me1R26me1 0.12% 0.09% 3.68E-01 K14me1R49me2 0.00% 0.00% 4.34E-01 K9me2R26me2 0.10% 0.10% 4.79E-01 K18me1K27ac 0.37% 0.29% 3.75E-01 R17me2K23me1 0.00% 0.00% 4.34E-01 K4me1R42me2 0.00% 0.00% 4.85E-01 K18me3R42me2 0.00% 0.00% 3.77E-01 R17me2K23me2 0.00% 0.00% 4.34E-01 R8me1R42me2 0.00% 0.00% 4.85E-01 K4me1K18me2 0.00% 0.00% 3.80E-01 R17me2R26me1 0.00% 0.00% 4.34E-01 R8me2R42me2 0.00% 0.00% 4.85E-01 R8me1K18me2 0.00% 0.00% 3.80E-01 R17me2R26me2 0.00% 0.00% 4.34E-01 K9me3R42me2 0.00% 0.00% 4.85E-01 R8me2K18me2 0.00% 0.00% 3.80E-01 R17me2K27me1 0.00% 0.00% 4.34E-01 K14me1R42me2 0.00% 0.00% 4.85E-01 K9me2K18me2 0.00% 0.00% 3.80E-01 R17me2K27me3 0.00% 0.00% 4.34E-01 R17me1R42me2 0.00% 0.00% 4.85E-01 K14me1K18me2 0.00% 0.00% 3.80E-01 R17me2K36me1 0.00% 0.00% 4.34E-01 R17me2R42me2 0.00% 0.00% 4.85E-01 R17me1K18me2 0.00% 0.00% 3.80E-01 R17me2K36me3 0.00% 0.00% 4.34E-01 K18me1R42me2 0.00% 0.00% 4.85E-01 R17me2K18me2 0.00% 0.00% 3.80E-01 R17me2K37me1 0.00% 0.00% 4.34E-01 K23me1R42me2 0.00% 0.00% 4.85E-01 K18me2R26me1 0.00% 0.00% 3.80E-01 R17me1R40me2 0.00% 0.00% 4.34E-01 K23me2R42me2 0.00% 0.00% 4.85E-01 K18me2R26me2 0.00% 0.00% 3.80E-01 R17me2R40me2 0.00% 0.00% 4.34E-01 R26me2R42me2 0.00% 0.00% 4.85E-01 K18me2R40me2 0.00% 0.00% 3.80E-01 R17me1R49me2 0.00% 0.00% 4.34E-01 K27me3R42me2 0.00% 0.00% 4.85E-01 K18me2R49me2 0.00% 0.00% 3.80E-01 R17me2R49me2 0.00% 0.00% 4.34E-01 K36me1R42me2 0.00% 0.00% 4.85E-01 K9me2K37me3 0.16% 0.20% 3.84E-01 K18me1K27me3 0.00% 0.00% 4.34E-01 K36me2R42me2 0.00% 0.00% 4.85E-01 K14acK23ac 2.65% 2.97% 3.86E-01 K18me1K36me1 0.00% 0.00% 4.34E-01 K36me3R42me2 0.00% 0.00% 4.85E-01 K23acK27ac 0.33% 0.43% 3.88E-01 K18me1K37me1 0.00% 0.00% 4.34E-01 K37me1R42me2 0.00% 0.00% 4.85E-01 K14me1K23me1 0.09% 0.06% 3.89E-01 K18me1R40me2 0.00% 0.00% 4.34E-01 R40me2R42me2 0.00% 0.00% 4.85E-01 R8me1K23me1 0.02% 0.02% 3.90E-01 K18me1R49me2 0.00% 0.00% 4.34E-01 R26me2K27me2 0.04% 0.04% 4.91E-01 K18me3R40me1 0.00% 0.00% 3.91E-01 K23me1R26me1 0.00% 0.00% 4.34E-01 K23me3K37me3 0.00% 0.00% 4.96E-01 K14me3K36me2 0.17% 0.14% 3.96E-01 K23me1R26me2 0.00% 0.00% 4.34E-01 K4acR8me2 0.00% 0.00% NA K23me1K27ac 0.23% 0.20% 3.97E-01 K23me2K36me3 0.00% 0.00% 4.34E-01 K4acR8me1 0.05% 0.00% NA K18me3K37me2 0.00% 0.00% 4.00E-01 K23me2K37me1 0.00% 0.00% 4.34E-01 K4me2R8me2 0.00% 0.00% NA K23me3R42me1 0.00% 0.00% 4.02E-01 K23me1R40me2 0.00% 0.00% 4.34E-01 K4me3R8me1 0.00% 0.00% NA K23me2K36ac 0.01% 0.02% 4.03E-01 K23me2R40me2 0.00% 0.00% 4.34E-01 K4me3R8me2 0.00% 0.00% NA R40me1R42me1 0.22% 0.28% 4.03E-01 K23me2R49me2 0.00% 0.00% 4.34E-01 K4me2R8me1 0.00% 0.00% NA K27acK36me2 0.23% 0.26% 4.04E-01 R26me1K27ac 0.00% 0.00% 4.34E-01 K4acK9ac 0.00% 0.00% NA R8me2K36ac 0.00% 0.00% 4.10E-01 R26me2K27me3 0.00% 0.00% 4.34E-01 K4acK9me2 0.00% 0.00% NA K9acK36ac 0.00% 0.00% 4.10E-01 R26me1R49me2 0.00% 0.00% 4.34E-01 K4acK9me3 0.00% 0.00% NA R17me2K36ac 0.00% 0.00% 4.10E-01 R26me2R49me2 0.00% 0.00% 4.34E-01 K4acK9me1 0.08% 0.00% NA K27acK36ac 0.00% 0.00% 4.10E-01 K36me1R40me2 0.00% 0.00% 4.34E-01 K4me3K9me1 0.00% 0.00% NA K36acK37me1 0.00% 0.00% 4.10E-01 K36me2R40me2 0.00% 0.00% 4.34E-01 K4me2K9me2 0.00% 0.00% NA K36acR40me2 0.00% 0.00% 4.10E-01 K36me3R40me2 0.00% 0.00% 4.34E-01 K4me3K9me2 0.00% 0.00% NA K36acR49me2 0.00% 0.00% 4.10E-01 K36me1R49me2 0.00% 0.00% 4.34E-01 K4me3K9me3 0.00% 0.46% NA K14acR17me1 0.20% 0.23% 4.18E-01 K36me2R49me2 0.00% 0.00% 4.34E-01 K4me2K9me3 0.00% 0.00% NA K37me3R42me2 0.00% 0.00% 4.19E-01 K36me3R49me2 0.00% 0.00% 4.34E-01 K4me2K9ac 0.00% 0.00% NA K14acK23me1 0.24% 0.21% 4.22E-01 K37me1R40me2 0.00% 0.00% 4.34E-01 K4me2K9me1 0.00% 0.00% NA K23acR49me2 0.25% 0.29% 4.22E-01 R40me2R49me2 0.00% 0.00% 4.34E-01 K4me3K9ac 0.00% 0.00% NA R40me1R42me2 0.00% 0.00% 4.27E-01 R8me2K9ac 0.00% 0.00% 4.34E-01 K4acK14me1 0.00% 0.00% NA K4me1R17me2 0.00% 0.00% 4.34E-01 R8me2K9me1 0.00% 0.00% 4.34E-01 K4acK14ac 0.00% 0.00% NA K4me1K18me1 0.00% 0.00% 4.34E-01 R8me2K9me2 0.00% 0.00% 4.34E-01 K4acK14me3 0.00% 0.00% NA K4me1K23me1 0.00% 0.00% 4.34E-01 R8me1K9me3 0.00% 0.00% 4.34E-01 K4me3K14me1 0.00% 0.00% NA K4me1K23me2 0.00% 0.00% 4.34E-01 R8me2K9me3 0.00% 0.00% 4.34E-01 K4me2K14me1 0.00% 0.15% NA K4me1R26me2 0.00% 0.00% 4.34E-01 R8me1K27me2 4.86% 5.01% 4.42E-01 K4me3K14me3 0.00% 0.00% NA K4me1R40me2 0.00% 0.00% 4.34E-01 K18me2R40me1 0.00% 0.00% 4.45E-01 K4me2K14ac 0.00% 0.13% NA K4me1R49me2 0.00% 0.00% 4.34E-01 K18me2R42me1 0.00% 0.00% 4.45E-01 K4me2K14me3 0.00% 0.00% NA R8me2K14me1 0.00% 0.00% 4.34E-01 R26me2K36ac 0.02% 0.02% 4.47E-01 K4me3K14ac 0.15% 0.00% NA R8me2R17me1 0.00% 0.00% 4.34E-01 R8me1K37me1 0.05% 0.06% 4.47E-01 K4me3K14me2 0.00% 0.00% NA R8me1R17me2 0.00% 0.00% 4.34E-01 K9acK36me1 0.12% 0.14% 4.53E-01 K4acK14me2 0.00% 0.00% NA 29 Binary co-existence Table S5 - continues Binary co-existence Wild type K4me2K14me2 Suz12-/- t-test Wild type Suz12-/- t-test 0.00% NA K4me3K27me3 Binary co-existence 0.00% 0.00% NA K4me2R49me1 Binary co-existence Wild type Suz12-/- t-test 0.00% NA K4acR17me1 0.00% 0.00% NA K4me2K27me3 0.15% 0.00% NA R8me1R49me1 0.00% 0.00% NA K4acR17me2 0.00% 0.00% NA K4me2K27me1 0.00% 0.22% NA R8me2R49me1 0.00% 0.00% NA K4me2R17me1 0.00% 0.00% NA K4me3K27ac 0.00% 0.00% NA K9me3R49me1 0.00% 0.00% NA K4me3R17me1 0.00% 0.00% NA K4me2K27ac 0.00% 0.00% NA K9acR49me1 0.00% 0.00% NA K4me2R17me2 0.00% 0.00% NA K4acK36me3 0.08% 0.00% NA K9me2R49me1 0.03% 0.10% NA K4me3R17me2 0.00% 0.00% NA K4acK36ac 0.00% NA K9me1R49me1 0.05% 0.05% NA K4acK18ac 0.00% 0.00% NA K4acK36me2 0.05% 0.00% NA K14me2K18me2 0.00% 0.00% NA K4acK18me2 0.00% 0.00% NA K4acK36me1 0.00% 0.00% NA K14me2K36ac 0.00% 0.00% NA K4acK18me1 0.00% 0.00% NA K4me3K36me3 0.00% 0.00% NA K14me3K37me2 0.00% 0.00% NA K4me3K18me2 0.00% 0.00% NA K4me2K36me3 0.00% 0.24% NA K14me2K37me2 0.00% 0.00% NA K4me2K18me2 0.00% 0.00% NA K4me2K36ac 0.00% 0.00% NA K14me2K37me3 0.00% 0.00% NA K4me3K18me1 0.00% 0.00% NA K4me3K36me2 0.33% 0.46% NA K14me2R40me1 0.00% 0.00% NA K4me2K18me1 0.00% 0.00% NA K4me3K36ac 0.00% 0.00% NA K14acR49me1 0.00% 0.03% NA K4me2K18me3 0.00% 0.00% NA K4me2K36me1 0.15% 0.13% NA K14me1R49me1 0.00% 0.00% NA K4me3K18ac 0.00% 0.00% NA K4me2K36me2 0.00% 0.00% NA K14me2R49me1 0.00% 0.00% NA K4me3K18me3 0.00% 0.00% NA K4me3K36me1 0.04% 0.00% NA K14me3R49me1 0.00% 0.00% NA K4me2K18ac 0.00% 0.13% NA K4acK37me3 0.00% 0.00% NA R17me1R49me1 0.00% 0.00% NA K4acK18me3 0.00% 0.00% NA K4acK37me1 0.00% 0.00% NA R17me2R49me1 0.00% 0.00% NA K4acK23me1 0.00% 0.00% NA K4me3K37me1 0.00% 0.00% NA K18acR49me1 0.00% 0.00% NA K4acK23ac 0.00% 0.00% NA K4me2K37me1 0.15% 0.13% NA K18me1R49me1 0.00% 0.00% NA K4acK23me3 0.00% 0.00% NA K4me3K37me3 0.00% 0.00% NA K18me3R49me1 0.00% 0.00% NA K4acK23me2 0.00% 0.00% NA K4me2K37me3 0.00% 0.00% NA K18me2R49me1 0.00% NA K4me3K23me3 0.00% NA K4me3K37me2 0.00% NA K23acR49me1 0.05% 0.03% NA K4me2K23me3 0.00% 0.00% NA K4me2K37me2 0.00% NA K23me1R49me1 0.00% 0.00% NA K4me3K23me1 0.00% 0.00% NA K4acK37me2 0.00% NA K23me3R49me1 0.00% 0.00% NA K4me3K23me2 0.00% 0.00% NA K4acR40me2 0.00% 0.00% NA K23me2R49me1 0.00% 0.00% NA K4me2K23me2 0.00% 0.00% NA K4me3R40me1 0.00% 0.00% NA R26me1R49me1 0.00% 0.00% NA K4me2K23ac 0.15% 0.24% NA K4me2R40me1 0.00% 0.00% NA R26me2R49me1 0.00% 0.00% NA K4me3K23ac 0.10% 0.00% NA K4acR40me1 0.00% 0.00% NA K27me2R49me1 0.00% 0.00% NA K4me2K23me1 0.00% 0.00% NA K4me3R40me2 0.00% 0.00% NA K27me3R49me1 0.03% 0.00% NA K4acR26me2 0.00% 0.00% NA K4me2R40me2 0.00% 0.00% NA K27acR49me1 0.05% 0.00% NA K4acR26me1 0.00% 0.00% NA K4acR42me2 0.00% 0.00% NA K27me1R49me1 0.00% 0.07% NA K4me3R26me1 0.00% 0.00% NA K4acR42me1 0.00% 0.00% NA K36me2R49me1 0.00% 0.00% NA K4me2R26me1 0.00% 0.00% NA K4me3R42me1 0.00% 0.00% NA K36me3R49me1 0.00% 0.00% NA K4me3R26me2 0.00% 0.00% NA K4me2R42me1 0.00% 0.00% NA K36me1R49me1 0.00% 0.07% NA K4me2R26me2 0.00% 0.00% NA K4me3R42me2 0.00% 0.00% NA K36acR49me1 0.00% NA K4acK27me1 0.00% 0.00% NA K4me2R42me2 0.00% NA K37me1R49me1 0.00% NA K4acK27me3 0.03% 0.00% NA K4acR49me2 0.00% 0.00% NA K37me2R49me1 0.00% NA K4acK27ac 0.00% 0.00% NA K4me3R49me2 0.00% 0.00% NA K37me3R49me1 0.00% NA K4acK27me2 0.05% 0.00% NA K4me2R49me2 0.00% 0.00% NA R40me2R49me1 0.00% NA K4me3K27me1 0.00% 0.00% NA K4me3R49me1 0.00% 0.00% NA R40me1R49me1 0.00% NA K4me3K27me2 0.37% 0.00% NA K4acR49me1 0.00% 0.00% NA R42me1R49me1 0.05% 0.05% NA K4me2K27me2 0.00% 0.00% NA K4me1R49me1 0.00% 0.00% NA R42me2R49me1 0.00% 0.00% NA 30 0.00% 0.00% Table S6 Binary co-existence Wild type Suz12-/- t-test Wild type Suz12-/- t-test Wild type Suz12-/- t-test 59.70% 5.64% 4.30E-07 K27me3R49me2 1.10% 0.01% 1.36E-01 R26me1K37me1 0.01% 0.01% 2.92E-01 K9me2K18ac 0.01% 2.63% 1.35E-04 K18me1K23me1 1.08% 0.01% 1.38E-01 K18acK27me2 2.25% 1.24% 3.02E-01 K9me1K27me2 31.66% 2.30% 2.26E-04 K9me1K23me1 0.55% 0.01% 1.40E-01 R17me1K23me1 0.01% 0.01% 3.05E-01 K9me3K27me2 10.23% 2.35% 2.84E-04 K14me1K23me1 0.55% 0.01% 1.40E-01 K14acR26me1 0.01% 0.01% 3.19E-01 K27me2K36me1 9.46% 0.20% 3.96E-04 K23me1K27me1 0.55% 0.01% 1.40E-01 K9acR49me2 0.01% 0.01% 3.26E-01 K14me1K27me2 14.20% 0.76% 7.01E-04 K9acK23me1 0.52% 0.01% 1.40E-01 K9me1R49me2 0.01% 0.01% 3.26E-01 K27me1K36me1 0.99% 10.20% 7.93E-04 K9me3K23me1 0.13% 0.01% 1.41E-01 K9me3R49me2 0.01% 0.01% 3.26E-01 K9me2K27me1 0.12% 11.83% 9.25E-04 K23me1K27me2 0.13% 0.01% 1.41E-01 K14me1R49me2 0.01% 0.01% 3.26E-01 K27me1K37me1 0.01% 2.00% 1.63E-03 K14acK23ac 0.32% 0.01% 1.41E-01 K18acR49me2 0.01% 0.01% 3.26E-01 K23acK27me2 16.49% 1.46% 1.73E-03 K9acR17me2 0.09% 0.01% 1.44E-01 K18me1R49me2 0.01% 0.01% 3.26E-01 K9me2K36me1 0.49% 17.09% 2.61E-03 K9me1K18me1 1.02% 0.37% 1.49E-01 K36me2R49me2 0.01% 0.01% 3.26E-01 K18acK36me1 0.01% 1.77% 3.69E-03 R17me2R26me1 0.01% 0.02% 1.49E-01 K36me3R49me2 0.01% 0.01% 3.26E-01 R26me2K27me2 1.26% 0.02% 5.30E-03 R17me2R26me2 0.01% 0.02% 1.49E-01 K37me1R49me2 0.01% 0.01% 3.26E-01 K9me2K36me3 1.04% 4.51% 8.79E-03 R17me2K27me3 0.01% 0.02% 1.49E-01 K14me3K23ac 0.50% 0.32% 3.38E-01 K9me2K37me1 0.23% 5.83% 1.11E-02 K9me1R17me1 1.34% 0.01% 1.50E-01 K23acK36me1 3.02% 3.66% 3.39E-01 K9me3K36me1 1.38% 0.21% 1.14E-02 R8me1K37me1 0.01% 0.76% 1.57E-01 K14me1K36me2 17.63% 16.50% 3.61E-01 K9me2K23ac 1.24% 5.31% 1.19E-02 K23acK37me1 0.55% 1.05% 1.67E-01 K14me1K23ac 3.89% 4.70% 3.67E-01 K9me3R26me1 1.16% 0.01% 1.24E-02 K9me2K27me3 2.52% 0.85% 1.70E-01 K18me1K23ac 0.65% 0.87% 3.69E-01 K36me1K37me1 1.05% 5.63% 1.50E-02 K9me2K14me1 0.01% 0.41% 1.79E-01 R17me1R49me2 0.01% 0.01% 3.78E-01 K27me1K36me2 1.77% 0.01% 1.87E-02 K9me1K27me1 0.28% 0.01% 1.79E-01 K9me3K23ac 0.47% 0.74% 3.82E-01 K9acK27me1 0.01% 0.47% 1.89E-02 K14me1K27me1 0.28% 0.01% 1.79E-01 R26me1K27me1 0.79% 0.62% 3.87E-01 K9acK36me1 0.01% 0.47% 1.89E-02 K18me1K27me1 0.28% 0.01% 1.79E-01 R17me1K23ac 0.44% 0.25% 3.93E-01 K9me1K36me3 2.19% 0.05% 1.98E-02 K18acK36me3 0.01% 0.46% 1.79E-01 K14me1K18me1 1.37% 1.22% 3.95E-01 K9acK37me1 0.01% 0.46% 2.10E-02 R8me1K9me2 0.01% 1.03% 1.80E-01 K18acK23ac 1.34% 1.02% 3.95E-01 K18acK27me1 0.20% 1.72% 2.11E-02 K14acR26me2 0.01% 0.02% 1.81E-01 K9acK14me3 0.34% 0.25% 3.96E-01 R8me1K27me2 2.15% 0.59% 2.37E-02 K9me3K14me3 0.26% 0.01% 1.83E-01 R17me2K36me2 0.68% 1.03% 4.07E-01 R8me1K36me2 2.15% 0.59% 2.37E-02 K9me3K14me1 0.01% 0.07% 1.83E-01 K18acK36me2 1.75% 2.15% 4.09E-01 K9me3K36me2 8.85% 5.30% 2.39E-02 K9me2K14me3 0.01% 0.32% 1.86E-01 K27me1K36me3 0.64% 0.78% 4.16E-01 K14me1K18ac 0.01% 1.69% 2.54E-02 R8me1K23me1 0.01% 0.01% 1.86E-01 K9me1K14me3 0.01% 0.01% 4.30E-01 K23acK27me3 1.41% 0.30% 3.06E-02 K18acK23me1 0.01% 0.01% 1.86E-01 K14me3K18ac 0.01% 0.01% 4.30E-01 K23acK36me2 12.96% 5.99% 3.61E-02 K23me1K36me3 0.01% 0.01% 1.86E-01 K14me3K18me1 0.01% 0.01% 4.30E-01 K14acK18me1 0.48% 0.01% 3.78E-02 K23me1K36me1 0.01% 0.01% 1.86E-01 K14me3K27me1 0.01% 0.01% 4.30E-01 R26me1K36me2 2.56% 0.01% 3.95E-02 K23me1K37me1 0.01% 0.01% 1.86E-01 K14me3K36me1 0.01% 0.01% 4.30E-01 R26me1K27me2 2.32% 0.01% 4.34E-02 K14acK27me3 0.67% 0.01% 1.87E-01 K14me3K36me3 0.01% 0.01% 4.30E-01 R17me1K36me2 2.09% 0.01% 4.56E-02 K18me1K36me2 2.02% 1.37% 1.90E-01 K14me3K37me1 0.01% 0.01% 4.30E-01 K18me1K27me2 0.89% 0.01% 4.66E-02 R8me1R26me1 0.01% 0.01% 1.92E-01 K14acK27me2 0.65% 0.55% 4.31E-01 K9me1K36me2 34.45% 26.12% 4.72E-02 R8me1K27me3 0.01% 0.01% 1.92E-01 K14acK36me2 0.65% 0.55% 4.31E-01 K9me1K27me3 2.05% 0.17% 5.10E-02 K14me1K36me3 0.55% 0.05% 1.94E-01 K9acR17me1 0.01% 0.01% 4.33E-01 K14me3K27me2 0.83% 0.35% 5.46E-02 K9acK27me2 0.82% 0.19% 2.02E-01 K9me3R17me1 0.01% 0.01% 4.33E-01 K14me3K36me2 0.83% 0.35% 5.46E-02 K14acK36me3 0.01% 0.52% 2.17E-01 K14me1R17me1 0.01% 0.01% 4.33E-01 K9me2R26me1 0.12% 0.52% 5.52E-02 K14acK18ac 0.01% 0.63% 2.17E-01 R17me1K18ac 0.01% 0.01% 4.33E-01 R8me1R26me2 0.01% 0.02% 5.56E-02 K18me1K27me3 0.15% 0.01% 2.19E-01 R17me1K18me1 0.01% 0.01% 4.33E-01 K23me1R26me2 0.01% 0.02% 5.56E-02 K27me3K36me3 0.46% 0.01% 2.21E-01 R17me1K36me3 0.01% 0.01% 4.33E-01 K23me1R26me1 0.01% 0.02% 5.56E-02 K27me3K37me1 0.23% 0.01% 2.21E-01 K9acK18ac 0.01% 0.01% 4.38E-01 K23me1K27me3 0.01% 0.02% 5.56E-02 R26me1K36me3 0.35% 0.01% 2.21E-01 K9me3K18ac 0.01% 0.01% 4.38E-01 K27me3K36me2 3.34% 0.01% 6.09E-02 K9acK14me1 0.36% 0.87% 2.21E-01 K9me2K18me1 0.01% 0.01% 4.38E-01 K23acK27me1 0.76% 2.41% 6.18E-02 K9acK23ac 0.36% 0.87% 2.21E-01 K9me3K18me1 0.01% 0.01% 4.38E-01 K18acK37me1 0.01% 0.51% 6.50E-02 K23acR26me1 0.20% 0.01% 2.24E-01 K9me3K27me1 0.01% 0.01% 4.38E-01 K27me2K36me3 1.16% 0.01% 7.10E-02 R8me1R17me1 0.87% 0.09% 2.33E-01 K9me2K27me2 0.01% 0.01% 4.38E-01 R17me1K27me2 1.93% 0.01% 7.82E-02 K14me3R49me2 0.01% 0.01% 2.42E-01 K9me1K36me1 0.01% 0.01% 4.38E-01 K9me1K23ac 10.79% 4.13% 7.83E-02 K9me2K23me1 0.01% 0.95% 2.47E-01 K9me2K36me2 0.01% 0.01% 4.38E-01 K27me3K36me1 2.96% 0.71% 8.03E-02 K9me3K37me1 0.06% 0.02% 2.49E-01 K9acK36me3 0.01% 0.01% 4.38E-01 K9me2K14ac 0.31% 2.59% 8.22E-02 K9me2R17me2 0.01% 0.31% 2.49E-01 K9me3K36me3 0.01% 0.01% 4.38E-01 K23acR49me2 0.29% 0.01% 8.58E-02 R17me2K18ac 0.01% 0.31% 2.49E-01 K9me1K37me1 0.01% 0.01% 4.38E-01 K27me2R49me2 0.53% 0.01% 8.72E-02 R17me2K23ac 0.01% 0.17% 2.50E-01 K14me1K36me1 0.01% 0.01% 4.38E-01 R8me1K23ac 0.87% 0.01% 9.05E-02 R17me2K36me1 0.01% 0.17% 2.50E-01 K14me1K37me1 0.01% 0.01% 4.38E-01 R17me2K27me2 0.68% 0.01% 9.19E-02 R26me2K36me2 0.57% 0.02% 2.50E-01 K18me1K36me1 0.01% 0.01% 4.38E-01 K27me2K37me1 0.71% 0.01% 9.37E-02 R8me1K9me3 0.01% 0.01% 2.58E-01 K18me1K36me3 0.01% 0.01% 4.38E-01 K9me2R17me1 0.01% 0.16% 9.51E-02 R8me1K9ac 0.01% 0.01% 2.58E-01 K18me1K37me1 0.01% 0.01% 4.38E-01 R17me1K36me1 0.01% 0.16% 9.51E-02 R8me1K18me1 0.01% 0.01% 2.58E-01 K36me2K37me1 0.01% 0.01% 4.38E-01 R17me1K37me1 0.01% 0.16% 9.51E-02 R8me1K36me1 0.01% 0.01% 2.58E-01 K36me3K37me1 0.01% 0.01% 4.38E-01 K23me1K36me2 1.20% 0.01% 9.69E-02 R8me1K36me3 0.01% 0.01% 2.58E-01 K14acR17me1 0.01% 0.01% 4.40E-01 K14acK27me1 0.01% 1.16% 1.01E-01 R8me1K14me1 0.43% 0.21% 2.62E-01 K14me3R17me1 0.01% 0.01% 4.40E-01 R17me1K27me1 0.01% 0.09% 1.01E-01 R8me1K27me1 0.01% 0.05% 2.62E-01 K9acK14ac 0.01% 0.01% 4.41E-01 K9acR26me2 0.01% 0.02% 1.16E-01 K14acK37me1 0.13% 0.66% 2.63E-01 K23acK36me3 1.18% 1.29% 4.46E-01 K9me1R26me2 0.01% 0.02% 1.16E-01 R26me1K36me1 0.79% 0.41% 2.64E-01 K14me3R26me1 0.01% 0.01% 4.46E-01 K9me2R26me2 0.01% 0.02% 1.16E-01 K9me1K18ac 1.03% 1.75% 2.65E-01 K14me3K27me3 0.01% 0.01% 4.46E-01 K9me3R26me2 0.01% 0.02% 1.16E-01 K9me3K14ac 0.36% 0.19% 2.69E-01 K9me1K14me1 15.13% 14.76% 4.47E-01 K14me1R26me2 0.01% 0.02% 1.16E-01 R8me1K9me1 1.23% 0.64% 2.69E-01 K9me1K14ac 0.18% 0.22% 4.48E-01 K18me1R26me2 0.01% 0.02% 1.16E-01 K27me1R49me2 0.01% 0.12% 2.72E-01 K9me2R49me2 1.37% 1.23% 4.56E-01 R26me2K27me1 0.01% 0.02% 1.16E-01 K14acR49me2 0.01% 0.31% 2.74E-01 R26me1R49me2 0.01% 0.01% 4.57E-01 R26me2K27me3 0.01% 0.02% 1.16E-01 K36me1R49me2 0.01% 0.11% 2.80E-01 K9acK18me1 0.79% 0.87% 4.61E-01 R26me2K36me1 0.01% 0.02% 1.16E-01 K9acR26me1 0.01% 0.01% 2.92E-01 R8me1K18ac 0.06% 0.07% 4.80E-01 R26me2K36me3 0.01% 0.02% 1.16E-01 K9acK27me3 0.01% 0.01% 2.92E-01 K9me1R17me2 0.01% 0.01% 4.85E-01 R26me2K37me1 0.01% 0.02% 1.16E-01 K9me3K27me3 0.01% 0.01% 2.92E-01 K9me3R17me2 0.01% 0.01% 4.85E-01 K14acK36me1 0.13% 1.35% 1.23E-01 K14me1R26me1 0.01% 0.01% 2.92E-01 K14me1R17me2 0.01% 0.01% 4.85E-01 K18acR26me2 0.01% 0.18% 1.27E-01 K18acR26me1 0.01% 0.01% 2.92E-01 R17me2K18me1 0.01% 0.01% 4.85E-01 K23acR26me2 0.01% 0.18% 1.27E-01 K18me1R26me1 0.01% 0.01% 2.92E-01 R17me2K27me1 0.01% 0.01% 4.85E-01 K9me1R26me1 1.16% 0.01% 1.30E-01 K18acK27me3 0.01% 0.01% 2.92E-01 R17me2K36me3 0.01% 0.01% 4.85E-01 K14me1K27me3 1.52% 0.14% 1.34E-01 R26me1K27me3 0.01% 0.01% 2.92E-01 R17me2K37me1 0.01% 0.01% 4.85E-01 K27me2K36me2 Binary co-existence 31 Binary co-existence Table S6 - continues Binary co-existence Wild type Suz12-/- t-test Suz12-/- t-test 1.08% 1.05% 4.87E-01 K4me2K36me2 0.00% NA K9me2K18me3 0.02% K4me3R8me2 0.02% NA K4me2K36me1 0.00% NA K9me3K18me3 0.02% K4me1R8me2 0.02% NA K4me2K36me3 0.00% NA K9me1K18me2 0.00% 0.01% NA K4me3R8me1 0.02% NA K4me1K37me1 0.12% NA K9me2K18me2 0.00% 0.01% NA K4me1R8me1 0.01% NA K4me3K37me1 0.02% NA K9acK18me2 0.00% 0.01% NA K4me2R8me1 0.00% NA K4me2K37me2 1.69% NA K9me3K18me2 0.00% 0.01% NA K9acK36me2 Binary co-existence Wild type 0.02% Binary co-existence Wild type Suz12-/- t-test NA NA K4me1K9ac 0.02% 0.01% NA K4me2K37me1 0.00% NA K9acK23me3 0.02% 0.01% NA K4me1K9me1 0.02% 0.73% NA K4me1K37me2 0.01% NA K9me1K23me3 0.02% 0.30% NA K4me1K9me2 0.02% 0.01% NA K4me1K37me3 0.01% NA K9me2K23me3 0.02% 0.01% NA K4me1K9me3 0.02% 0.39% NA K4me2K37me3 0.00% NA K9me3K23me3 0.02% 0.01% NA K4me3K9me3 2.95% NA K4me3R40me2 0.02% NA K9me1K23me2 0.01% NA K4me3K9ac 0.02% NA K4me1R40me2 0.01% NA K9me3K23me2 0.01% NA K4me3K9me1 0.02% NA K4me2R40me2 0.00% NA K9me2K23me2 0.01% NA K4me3K9me2 0.02% NA K4me1R42me2 0.01% NA K9acK23me2 0.01% NA K4me2K9me2 0.00% NA K4me3R42me2 0.02% NA K9acK27ac 0.01% 0.02% NA K4me2K9me1 0.00% NA K4me2R42me1 0.00% NA K9me1K27ac 0.01% 1.10% NA K4me2K9ac 0.00% NA K4me2R42me2 0.00% NA K9me2K27ac 0.89% 0.02% NA K4me2K9me3 0.00% NA K4me1R42me1 0.00% NA K9me3K27ac 0.01% 0.02% NA 0.01% NA K9me3K36ac 0.60% NA K4me1K14ac 0.02% 0.01% NA K4me1R49me2 0.02% K4me1K14me1 0.02% 0.01% NA K4me3R49me2 0.02% NA K9acK36ac 0.02% NA K4me1K14me3 0.02% 0.01% NA K4me2R49me2 0.00% NA K9me1K36ac 0.02% NA K4me3K14me2 0.02% NA K4me2R49me1 0.00% NA K9me2K36ac 0.02% NA K4me3K14me1 0.02% NA K4me1R49me1 0.00% NA K9acK37me2 0.00% 0.01% NA K4me3K14ac 0.02% NA R8me2K9ac 0.01% NA K9me3K37me2 0.00% 0.01% NA K4me1K14me2 0.01% NA R8me2K9me1 0.01% NA K9me1K37me2 0.00% 0.01% NA K4me3K14me3 0.02% NA R8me2K9me2 0.01% NA K9me2K37me2 0.00% 0.01% NA K4me2K14me1 0.00% NA R8me2K9me3 0.01% NA K9acK37me3 0.01% NA K4me2K14me3 0.00% NA R8me1K14ac 0.00% 0.01% NA K9me3K37me3 0.01% NA K4me2K14ac 0.00% NA R8me1K14me2 0.00% 0.01% NA K9me2K37me3 2.11% NA K4me2K14me2 0.00% NA R8me1K14me3 0.00% 0.01% NA K9me1K37me3 0.01% NA K4me1R17me1 0.02% 0.01% NA R8me2K14me1 0.01% NA K9me1R40me2 0.01% NA K4me1R17me2 0.02% 0.01% NA R8me2K14me2 0.01% NA K9me2R40me2 0.62% NA K4me3R17me2 0.02% NA R8me2K14ac 0.50% NA K9me3R40me2 0.01% NA K4me3R17me1 0.02% NA R8me2K14me3 0.01% NA K9acR40me2 0.01% NA K4me2R17me2 0.00% NA R8me1R17me2 0.01% NA K9me1R40me1 0.00% NA K4me2R17me1 0.00% NA R8me2R17me2 0.02% NA K9me3R40me1 0.00% NA 0.02% NA K9acR40me1 0.00% NA 0.01% NA K9me2R40me1 0.00% NA 0.01% K4me1K18ac 0.02% 0.01% NA R8me2R17me1 K4me1K18me1 0.02% 0.01% NA R8me1K18me2 K4me1K18me3 0.02% NA R8me2K18me2 0.01% NA K9me1R42me1 0.01% 0.00% NA 0.00% K4me3K18me1 0.02% NA R8me2K18me1 0.01% NA K9me3R42me1 0.01% 0.00% NA K4me1K18me2 0.01% NA R8me2K18ac 1.04% NA K9me2R42me1 0.01% 0.00% NA K4me3K18ac 0.02% NA R8me2K23ac 0.01% NA K9acR42me1 0.01% 0.00% NA K4me3K18me2 0.02% NA R8me2K23me3 0.02% NA K9me1R42me2 0.01% 0.01% NA K4me2K18me1 0.00% NA R8me1K23me3 0.01% NA K9me2R42me2 0.01% 0.14% NA K4me2K18me2 0.00% NA R8me2K23me1 0.02% NA K9me3R42me2 0.01% 0.01% NA K4me2K18ac 0.65% NA R8me2K23me2 0.02% NA K9acR42me2 0.01% 0.01% NA K4me1K23ac 0.02% 0.73% NA R8me1K23me2 0.01% NA K9acR49me1 0.01% 0.00% NA K4me1K23me3 0.02% 0.01% NA R8me2R26me1 0.01% NA K9me3R49me1 0.01% 0.73% NA K4me3K23ac 2.95% NA R8me2R26me2 0.02% NA K9me2R49me1 0.38% 0.00% NA K4me3K23me3 0.02% NA R8me1K27ac 0.02% NA K9me1R49me1 0.01% 0.00% NA K4me3K23me1 0.02% NA R8me2K27me1 0.01% NA K14acR17me2 0.02% 0.01% NA K4me1K23me1 0.01% NA R8me2K27me3 0.01% NA K14me3R17me2 0.02% 0.01% NA K4me3K23me2 0.02% NA R8me2K27ac 0.02% NA K14me2R17me1 0.00% 0.01% NA K4me1K23me2 0.01% NA R8me2K27me2 0.93% NA K14me2R17me2 0.01% NA K4me2K23me1 0.00% NA R8me2K36me1 0.01% NA K14acK18me3 0.02% NA K4me2K23ac 1.04% NA R8me2K36me3 0.61% NA K14me1K18me3 0.02% NA K4me2K23me2 0.00% NA R8me2K36ac 0.02% NA K14me3K18me3 0.74% K4me2K23me3 0.00% NA R8me2K36me2 1.73% NA K14me2K18me1 0.00% 0.01% NA 0.02% NA K14me3K18me2 0.00% 0.01% NA 0.01% NA K14me2K18me2 0.00% 0.01% NA 0.01% NA K4me1R26me1 0.02% 0.02% NA R8me1K36ac K4me1R26me2 0.02% 0.02% NA R8me1K37me2 K4me3R26me2 0.02% NA R8me2K37me1 0.01% NA K14me1K18me2 0.00% 0.01% NA K4me3R26me1 0.02% NA R8me1K37me3 0.01% NA K14me2K18ac 0.00% 0.01% NA 0.00% K4me1K27ac 0.02% 0.02% NA R8me2K37me3 0.02% NA K14acK18me2 0.38% 0.01% NA K4me1K27me1 0.02% 0.01% NA R8me2K37me2 0.01% NA K14acK23me3 0.46% 0.76% NA K4me1K27me2 4.94% 0.01% NA R8me2R40me2 0.02% NA K14me1K23me3 0.02% 0.01% NA K4me1K27me3 0.02% 0.02% NA R8me1R40me2 0.01% NA K14me3K23me3 0.02% 0.01% NA K4me3K27me1 0.02% NA R8me2R40me1 0.00% NA K14me3K23me1 0.00% 0.01% NA K4me3K27me2 0.02% NA R8me1R40me1 0.00% NA K14acK23me1 0.00% 0.01% NA K4me3K27ac 0.02% NA R8me1R42me1 0.00% NA K14me2K23me1 0.00% 0.01% NA K4me3K27me3 0.02% NA R8me2R42me2 0.01% NA K14me2K23ac 0.21% 0.28% NA K4me2K27me2 0.00% NA R8me1R42me2 0.01% NA K14acK23me2 0.01% NA K4me2K27me1 1.69% NA R8me1R49me1 0.00% NA K14me1K23me2 0.01% NA 0.01% 0.01% K4me1K36me1 0.02% 0.12% NA R8me2R49me2 0.01% NA K14me2K23me2 0.01% NA K4me1K36me2 4.94% 1.71% NA R8me1R49me2 0.01% NA K14me2K23me3 0.01% NA K4me1K36me3 0.02% 0.01% NA K9me1K14me2 0.00% 0.37% NA K14me3K23me2 0.01% NA K4me3K36me3 0.02% NA K9me2K14me2 0.00% 0.01% NA K14me3R26me2 0.01% 0.02% NA K4me3K36me2 2.95% NA K9me3K14me2 0.00% 0.01% NA K14me2R26me2 0.00% 0.02% NA K4me3K36me1 0.02% NA K9acK14me2 0.00% 0.47% NA K14me2R26me1 0.00% 0.01% NA K4me3K36ac 0.02% NA K9acK18me3 0.02% NA K14acK27ac 0.01% 0.02% NA K4me1K36ac 0.02% NA K9me1K18me3 0.02% NA K14me1K27ac 0.01% 1.10% NA 32 Table S6 - continues Wild type Suz12-/- t-test K14me3K27ac Binary co-existence 0.01% 0.02% NA K18me2K23me2 Binary co-existence K14me2K27ac 0.21% 0.02% NA K18me3R26me1 K14me2K27me3 0.00% 0.01% NA K14me2K27me1 0.00% 0.70% K14me2K27me2 0.00% K14me2K36me1 Wild type Suz12-/- t-test Suz12-/- t-test 0.01% NA K23me1K37me3 Binary co-existence Wild type 0.01% NA 0.02% NA K23me3K37me2 0.01% NA K18me3R26me2 0.02% NA K23me2K37me2 0.01% NA NA K18me2R26me2 0.00% 0.02% NA K23acR40me2 0.01% NA 0.01% NA K18me2R26me1 0.00% 0.01% NA K23me3R40me2 0.01% NA 0.00% 0.98% NA K18acK27ac 0.01% 0.02% NA K23me1R40me2 0.01% NA K14me2K36me2 0.00% 0.01% NA K18me1K27ac 0.01% 0.02% NA K23me2R40me2 0.01% NA K14me2K36me3 0.00% 0.01% NA K18me3K27ac 0.02% NA K23acR40me1 0.00% NA K14me2K36ac 0.02% NA K18me3K27me1 0.02% NA K23acR42me1 0.01% 1.35% NA K14me3K36ac 0.02% NA K18me3K27me2 0.74% NA K23me1R42me1 0.01% 0.00% NA K14acK36ac 0.02% NA K18me3K27me3 0.02% NA K23acR42me2 0.01% 0.14% NA K14me1K36ac 0.02% NA K18me2K27me2 0.00% 0.01% NA K23me3R42me2 0.01% NA K14acK37me2 0.00% 0.01% NA K18me2K27me3 0.00% 0.01% NA K23me2R42me2 0.01% NA K14me2K37me2 0.00% 0.01% NA K18me2K27me1 0.00% 0.01% NA K23me1R42me2 0.01% NA K14me1K37me2 0.00% 0.01% NA K18me2K27ac 0.00% 0.02% NA K23me2R42me1 0.00% NA K14me3K37me2 0.00% 0.00% NA K18me3K36me1 0.02% NA K23me3R42me1 0.00% NA K14me2K37me1 0.00% 0.46% NA K18me3K36me2 0.74% NA K23me3R49me2 0.02% 0.01% NA K14acK37me3 1.02% NA K18me3K36me3 0.02% NA K23acR49me1 0.38% 0.00% NA K14me2K37me3 0.01% NA K18me2K36me3 0.00% 0.01% NA K23me1R49me1 0.01% 0.00% NA K14me3K37me3 0.00% NA K18me2K36me2 0.00% 0.01% NA K23me2R49me2 0.01% NA K14me1K37me3 0.01% NA K18me2K36me1 0.38% 0.01% NA K23me1R49me2 0.95% NA K14me1R40me2 0.01% NA K18me2K36ac 0.02% NA K23me3R49me1 0.00% NA K14acR40me2 0.01% NA K18me1K36ac 0.02% NA K23me2R49me1 0.00% NA K14me3R40me2 0.01% NA K18acK36ac 0.02% NA R26me1K27ac 0.01% 0.02% NA K14me2R40me2 0.01% NA K18me3K37me1 0.02% NA R26me2K27ac 0.01% 0.02% NA K14me3R40me1 0.00% NA K18acK37me2 0.00% 0.22% NA R26me1K36ac 0.02% NA K14me1R40me1 0.00% NA K18me1K37me2 0.00% 0.01% NA R26me2K36ac 0.02% NA K14me2R40me1 0.00% NA K18me2K37me2 0.00% 0.01% NA R26me1K37me2 0.00% 0.01% NA K14acR40me1 0.00% NA K18me2K37me1 0.38% 0.01% NA R26me2K37me2 0.00% 0.02% NA K14me1R42me1 0.01% 0.00% NA K18acK37me3 1.10% NA R26me2K37me3 0.02% NA K14me1R42me2 0.01% 0.01% NA K18me2K37me3 0.01% NA R26me1K37me3 0.02% NA K14acR42me2 0.01% 0.01% NA K18me1K37me3 0.01% NA R26me1R40me2 0.02% NA K14me3R42me2 0.01% 0.01% NA K18acR40me2 0.01% NA R26me2R40me2 0.02% NA K14me2R42me2 0.01% NA K18me2R40me2 0.01% NA R26me1R40me1 0.00% NA K14acR42me1 0.00% NA K18me1R40me2 0.01% NA R26me2R42me1 0.01% K14me2R42me1 0.00% NA K18me2R40me1 0.00% NA R26me1R42me1 0.01% K14me3R42me1 0.00% NA K18acR40me1 0.00% NA R26me1R42me2 0.01% 0.00% NA K18me1R40me1 0.00% NA R26me2R42me2 K14me2R49me2 0.01% NA K18acR42me1 0.01% 0.00% NA R26me2R49me2 0.02% K14acR49me1 0.00% NA K18me1R42me1 0.01% 0.00% NA R26me1R49me1 0.01% K14me3R49me1 0.00% NA K18acR42me2 0.01% 0.01% NA R26me2R49me1 0.01% K14me2R49me1 0.00% NA K18me1R42me2 0.01% 0.01% NA K27acK36me1 0.15% 0.02% NA K14me1R49me1 0.01% NA NA 0.01% NA 0.02% NA 0.02% NA NA NA R17me1K18me3 0.02% NA K18me2R42me2 0.01% NA K27acK36me2 0.01% 1.10% NA R17me2K18me3 0.02% NA K18me2R42me1 0.00% NA K27acK36me3 0.01% 0.02% NA R17me1K18me2 0.00% 0.01% NA K18me3R49me2 0.02% NA K27me1K36ac 0.02% NA 0.01% NA K18me1R49me1 0.01% 0.00% NA K27me3K36ac 0.02% NA 0.01% 0.00% NA K27me2K36ac 0.02% NA 0.02% NA R17me2K18me2 R17me1K23me3 0.02% 0.01% NA K18acR49me1 R17me2K23me3 0.02% 0.01% NA K18me2R49me2 0.01% NA K27acK36ac R17me2K23me1 0.01% 0.01% NA K18me2R49me1 0.00% NA K27acK37me1 0.01% 0.02% NA R17me2K23me2 0.01% NA K23me3R26me1 0.02% 0.02% NA K27me2K37me2 0.00% 0.01% NA R17me1K23me2 0.01% NA K23me3R26me2 0.02% 0.02% NA K27me1K37me2 0.00% 0.57% NA R17me1R26me1 0.97% 0.02% NA K23me2R26me1 0.02% NA K27acK37me2 0.00% R17me1R26me2 0.01% 0.02% NA K23me2R26me2 0.02% NA K27me3K37me2 0.00% R17me1K27ac 0.01% 0.02% NA K23acK27ac 0.95% 1.10% NA R17me2K27ac 0.01% 0.02% NA K23me3K27ac 0.02% 0.02% R17me1K27me3 0.01% 0.02% NA K23me3K27me1 0.02% R17me2K36ac 0.02% NA K23me3K27me2 R17me1K36ac 0.02% NA 0.00% R17me1K37me3 NA 0.01% NA K27me1K37me3 1.10% NA NA K27me2K37me3 0.01% NA 0.01% NA K27me3K37me3 0.02% NA 0.02% 0.01% NA K27me2R40me2 0.01% NA K23me3K27me3 0.02% 0.02% NA K27me1R40me2 0.62% NA NA K23me1K27ac 0.01% 0.02% NA K27me3R40me2 0.02% NA 0.00% NA K23me2K27me1 0.01% NA K27acR40me2 0.02% NA R17me2K37me2 0.01% NA K23me2K27me2 0.01% NA K27me2R40me1 0.00% NA R17me2K37me3 0.01% NA K23me2K27ac 0.02% NA K27me3R40me1 0.00% NA R17me1R40me2 0.01% NA K23me2K27me3 0.02% NA K27me1R40me1 0.00% NA R17me2R40me2 0.01% NA K23me3K36me1 0.02% 0.01% NA K27acR42me1 0.01% R17me1K37me2 0.00% NA R17me2R42me1 0.01% 0.00% NA K23me3K36me2 0.02% 0.01% NA K27me1R42me1 0.01% 0.00% NA R17me1R42me1 0.01% 0.00% NA K23me3K36me3 0.02% 0.01% NA K27me2R42me1 0.01% 0.00% NA R17me1R42me2 0.01% 0.01% NA K23me1K36ac 0.02% NA K27me3R42me1 0.01% 0.01% NA K23acK36ac 0.02% NA K27me2R42me2 0.01% 0.44% NA R17me2R42me2 NA R17me2R49me2 0.02% 0.01% NA K23me3K36ac 0.02% NA K27me3R42me2 0.01% 0.01% NA R17me1R49me1 0.01% 0.00% NA K23me2K36me3 0.01% NA K27me1R42me2 0.01% 0.26% NA R17me2R49me1 0.01% 0.00% NA K23me2K36me2 0.01% NA K27acR42me2 0.01% 0.02% NA K18me3K23ac 0.74% NA K23me2K36me1 0.01% NA K27acR49me2 0.29% 0.02% NA K18acK23me3 0.02% 0.01% NA K23me2K36ac 0.02% NA K27acR49me1 0.38% K18me1K23me3 0.02% 0.01% NA K23me3K37me1 0.02% 0.01% NA K27me1R49me1 0.01% K18me3K23me3 0.02% NA K23acK37me2 0.31% 0.67% NA K27me3R49me1 0.43% K18me2K23me1 0.00% 0.01% NA K23me1K37me2 0.00% 0.01% NA K27me2R49me1 0.01% 0.00% NA K18me2K23ac 0.38% 0.01% NA K23me2K37me1 0.01% NA K36me3K37me2 0.00% 0.01% NA K18acK23me2 0.01% NA K23me2K37me3 0.01% NA K36me1K37me2 0.00% 0.49% NA K18me1K23me2 0.01% NA K23acK37me3 0.01% NA K36me2K37me2 0.00% 0.01% NA K18me2K23me3 0.01% NA K23me3K37me3 0.01% NA K36acK37me1 0.02% NA 33 NA 0.00% NA NA Table S6 - continues Suz12-/- t-test K36me2K37me3 Binary co-existence Wild type 0.01% NA K36acR42me2 Binary co-existence K36me3K37me3 1.02% NA K36me2R49me1 K36me1K37me3 1.10% NA K36me3R40me2 0.01% K36me1R40me2 Wild type Suz12-/- t-test 0.02% NA K37me1R49me1 Binary co-existence Wild type Suz12-/- t-test 0.01% 0.00% 0.01% 0.00% NA NA K37me3R49me1 0.00% K36me1R49me1 0.01% 0.00% NA NA K37me2R49me1 0.00% NA K36me3R49me1 0.01% NA 0.00% NA K37me2R49me2 0.01% 0.01% NA NA K36acR49me2 0.02% NA K37me3R49me2 0.01% K36me2R40me2 0.01% NA NA K37me1R40me2 0.01% NA R40me2R42me2 0.01% K36acR40me2 NA 0.02% NA K37me3R40me2 0.01% NA R40me2R42me1 0.00% NA K36me1R40me1 0.00% NA K37me2R40me2 0.01% NA R40me1R42me2 1.30% NA K36me2R40me1 0.00% NA K37me1R40me1 0.00% NA R40me2R49me2 0.01% NA K36me3R40me1 0.00% NA K37me2R40me1 0.00% NA R40me2R49me1 0.00% NA 0.00% NA K36me2R42me1 0.01% 0.00% NA K37me1R42me1 0.01% 0.00% NA R40me1R49me2 K36me1R42me1 0.01% 0.00% NA K37me1R42me2 0.01% 0.01% NA R42me1R49me1 0.01% 0.00% NA K36me3R42me1 0.01% 0.00% NA K37me3R42me1 0.00% NA R42me2R49me2 0.01% 0.28% NA K36me3R42me2 0.01% 0.01% NA K37me2R42me2 0.01% NA R42me2R49me1 0.00% NA K36me1R42me2 0.01% 0.40% NA K37me2R42me1 0.00% NA R42me1R49me2 0.00% NA K36me2R42me2 1.58% 0.01% NA K37me3R42me2 0.01% NA 34 Table S7 and S8 Table S7 Histone H4 Histone code Table S8 Wild type Suz12-/- Wild type Suz12-/- 2.32% 0.86% S1ac 90.60% 91.41% K5acK20me1 0.35% 2.08% K5acK20me2 11.12% 6.28% K5ac 5.86% 4.43% K13me1 0.64% B.D.L. K5acK20me3 0.38% 0.17% R3me1 0.57% 0.32% S1ac 15.08% 15.46% K5acK36me1 0.37% 0.14% S1acK12ac 0.24% 0.39% S1acK15me1 1.09% 2.32% S1acK12acK20me2 1.73% 1.02% K9me1 0.21% B.D.L. S1acK12acR23me2 0.26% B.D.L. (unmodified) 0.25% B.D.L. S1acK16ac 2.30% 2.26% S1acR17me1 0.15% 0.33% S1acK16acK20me1 0.53% 0.50% S1acK5ac 0.13% 0.05% S1acK16acK20me2 4.44% 8.34% S1acK5acK15me1 0.05% B.D.L. S1acK20me1 9.21% 6.53% S1acK9acR17me1 0.03% B.D.L. S1acK20me2 47.93% 50.38% K5acK9ac 0.03% B.D.L. S1acK20me3 3.41% 3.18% K5acR32me1 0.02% B.D.L. S1acR17me2 0.70% B.D.L. S1acK9ac 0.01% B.D.L. K5acR19me1K20me2 B.D.L. 0.09% S1acK9acK15me1 0.00% B.D.L. S1acK16acR23me2 B.D.L. 1.12% K5acR29me1 B.D.L. 0.15% S1acK20me1R23me1 B.D.L. 0.54% S1acR29me2 B.D.L. 0.13% S1acK5ac B.D.L. 0.11% K5acR20me1 B.D.L. 0.07% S1acK8ac B.D.L. 0.05% S1acK5acR17me1 B.D.L. 0.02% S1acK8acK12ac B.D.L. 0.15% S1acK8acK20me2 B.D.L. 0.43% S1acR23me2 B.D.L. 0.06% K5ac Histone code Histone H2A Table S9 Wild type - 1 in Histone database 290 0 0.00% Wild type - 2 323 0 0.00% Wild type - 3 318 0 0.00% Wild type - 4 307 0 0.00% Suz12 - 1 300 0 0.00% Suz12 - 2 298 0 0.00% Suz12 - 3 327 0 0.00% Suz12 - 4 293 0 0.00% in Decoy FDR Above identity threshold in Decoy FDR Wild type - 1 in Histone database 293 0 0.00% Wild type - 2 327 0 0.00% Wild type - 3 323 0 0.00% Wild type - 4 313 0 0.00% Suz12 - 1 308 0 0.00% Suz12 - 2 304 0 0.00% Suz12 - 3 337 0 0.00% Suz12 - 4 300 0 0.00% above identity or homology threshold 35 Table S10 K27 K36 unmod me1 me2 me3 ac unmod unmod unmod unmod unmod Jung et al.* Middle-down Suz12-/WT Suz12-/- WT Suz12-/WT Suz12-/-/- Suz12-/- WT Suz12-/- unmod me1 me2 me3 ac me1 me1 me1 me1 me1 unmod me1 me2 me3 ac me2 me2 me2 me2 me2 unmod me1 me2 me3 ac me3 me3 me3 me3 me3 Suz12-/- unmod me1 me2 me3 ac ac ac ac ac ac Suz12-/- Suz12 Suz12-/WT WT Suz12-/- WT Suz12-/- Suz12-/WT WT WT WT WT Suz12-/- Suz12-/- Suz12-/WT WT Suz12-/- 36 Table S11 K4me1 K4me2 K4me3 K4ac R8me1 R8me2 K9me1 K9me2 K9me3 K9ac K14me1 H3.2 wild type 2.13% 0.03% 0.13% 0.09% 5.08% 0.80% H3.2 Suz12-/- 5.52% 0.13% 0.08% 0.00% 6.20% 0.57% 41.25% 5.09% 11.01% 3.32% 22.65% 30.87% 39.34% 6.16% 1.58% H3.3 wild type 1.62% 0.00% 0.00% 0.00% 4.25% 16.27% 0.26% 19.19% 10.92% 11.64% 7.81% 8.24% H3.3 Suz12-/- 2.65% 0.00% 0.00% 0.00% 1.09% 0.06% 17.26% 39.06% 22.36% 2.21% 9.99% wild type (t-test) 27.59% 17.04% 8.14% Suz12-/- (t-test) 1.38% 10.77% 17.04% 4.52% 33.77% 5.87% 0.01% 6.60% 40.31% 8.96% 0.00% N.A. 0.00% 0.32% 0.01% 48.01% 1.00% 32.35% 1.14% K14me2 K14me3 K14ac R17me1 R17me2 K18me1 K18me2 K18me3 K18ac K23me1 K23me2 H3.2 wild type 0.02% 0.13% 16.15% 1.52% 0.62% 3.96% 0.11% 0.01% 10.77% 1.04% 0.65% H3.2 Suz12-/- 0.91% 0.36% 18.44% 1.17% 0.74% 2.81% 1.11% 0.07% 8.91% 0.65% 0.27% H3.3 wild type 0.00% 0.85% 18.35% 0.83% 1.88% 4.79% 1.17% 0.59% 12.78% 0.83% 9.85% H3.3 Suz12-/- 0.59% 4.96% 15.20% 1.81% 0.17% 4.33% 0.21% 0.61% 9.66% 2.27% 1.50% wild type (t-test) 10.53% 10.45% 33.11% 21.05% 17.83% 30.35% 4.86% 0.95% 34.98% 33.21% 0.69% Suz12-/- (t-test) 29.42% 3.93% 30.16% 20.77% 1.11% 24.33% 1.05% 7.51% 43.97% 7.03% 12.58% K23me3 K23ac R26me1 R26me2 K27me1 K27me2 K27me3 K27ac K36me1 K36me2 K36me3 H3.2 wild type 0.86% 28.66% 2.25% 0.44% 6.38% 82.10% 5.26% 0.94% 9.12% 77.48% 2.34% H3.2 Suz12-/- 0.24% 23.30% 1.54% 0.11% 19.77% 16.62% 1.40% 0.99% 24.32% 38.69% 7.73% H3.3 wild type 10.87% 31.75% 2.75% 1.22% 6.56% 59.46% 18.79% 3.99% 11.12% 61.23% 3.44% H3.3 Suz12-/- 6.38% 29.31% 1.19% 1.46% 16.30% 3.75% 3.20% 1.84% 28.99% 41.23% 6.83% wild type (t-test) 1.85% 36.10% 38.20% 22.17% 45.34% 0.05% 0.48% 12.47% 12.54% 0.40% 24.68% Suz12-/- (t-test) 2.70% 15.88% 29.98% 9.97% 20.18% 0.01% 13.00% 15.21% 16.53% 31.54% 34.06% K36ac K37me1 K37me2 K37me3 R40me1 R40me2 R42me1 R42me2 R49me1 R49me2 H3.2 wild type 0.26% 3.14% 0.01% 0.12% 0.19% 0.43% 0.15% 0.28% 0.01% 0.44% H3.2 Suz12-/- 0.50% 11.97% 0.03% 0.17% 0.87% 5.38% 0.56% 1.23% 0.16% 1.09% H3.3 wild type 0.37% 2.71% 0.00% 0.15% 0.23% 1.02% 0.20% 0.13% 0.00% 0.26% H3.3 Suz12-/- 1.88% 8.11% 0.04% 0.30% 0.10% 0.27% 0.14% 0.68% 0.04% 0.80% wild type (t-test) 38.81% 32.81% 9.51% 42.21% 39.74% 28.62% 35.69% 14.36% 17.04% 11.02% Suz12-/- (t-test) 3.69% 4.65% 45.40% 33.66% 2.61% 0.00% 8.63% 9.97% 9.87% 34.90% 37