Figure S1. An illustration of the study design
3 Species
8 Samples
per species
RNAseq+
5 ChIPseq
Human
Chimpanzee
Rhesus Macaque
4 male, 4 female LCLs
5 male, 3 female LCLs
6 male, 2 female LCLs
Expression:
RNAseq
Active Gene
Marks:
Enhancer Marks:
Pol II (ChIPseq)
H3K4me1
(ChIPseq)
H3K4me3
(ChIPseq)
H3K27ac
(ChIPseq)
Repressed
Region
Mark:
H3K27me3
(ChIPseq)
Figure S2. Choices of cutoffs for classifying regions as enriched
Figure S3. Pairwise Spearman’s rank correlations between
individuals from the three primates for four histone marks, Pol II
and RNA
H3K4me1
H3K4me3
H3K27ac
H3K27me3
PolII
RNA
H
C
R
H
C
R
H
C
R
Fold Enrichment, TSS +/- 10 kb
Figure S4. Fold enrichment of the five marks in regions near
TSSs in three primates
A
Human
Chimpanzee
Rhesus Macaque
Human
Chimpanzee
Rhesus Macaque
Fold Enrichment, TSS +/- 50 kb
B
H3K4me1
H3K4me3
H3K27ac
H3K27me3
Pol II
Figure S5. Pairwise Spearman’s rank correlations between
marks in each of the three primates
-0.4
0.0
0.3
0.7
TSS +/- 50 kb
TSS +/- 10 kb
TSS +/- 2 kb
Chimpanzee
1.0
Human
Rhesus Macaque
Figure S6. Mark enrichment levels are correlated with gene
expression levels in chimpanzee
Medium Expressed
High Expressed
Distance to TSS (kb)
Distance to TSS (kb)
Distance to TSS (kb)
R2
Scaled Enrichment Level
Enrichment Level
Low Expressed
Gene Expression Level
H3K4me1
marginal
TSS +/- 2kb
H3K4me3
H3K27ac
marginal + interactions
TSS +/- 10kb
H3K27me3
TSS +/- 50kb
Pol II
Figure S7. Mark enrichment levels are correlated with gene
expression levels in rhesus macaque
Medium Expressed
High Expressed
Distance to TSS (kb)
Distance to TSS (kb)
Distance to TSS (kb)
R2
Scaled Enrichment Level
Enrichment Level
Low Expressed
Gene Expression Level
H3K4me1
marginal
TSS +/- 2kb
H3K4me3
H3K27ac
marginal + interactions
TSS +/- 10kb
H3K27me3
TSS +/- 50kb
Pol II
Figure S8. Mark enrichment levels are plotted against gene
expression levels for sliding windows of genes ordered by
increasing expression levels in the three primates
Chimpanzee
Rhesus Macaque
TSS +/- 50 kb
Scaled Enrichment Level
TSS +/- 10 kb
Scaled Enrichment Level
Human
Gene Expression Level
H3K4me1
Gene Expression Level
H3K4me3
H3K27ac
Gene Expression Level
H3K27me3
Pol II
Predicted Gene Expression Level
Figure S9. Scatterplot of predicted gene expression levels
against true gene expression levels for all analyzed genes in
human
H3K4me1
True Gene Expression Level
H3K4me3
H3K27me3
H3K27ac
Pol II
marginal
Figure S10. Importance of the marginal and first-order interaction
effects from the five marks for explaining gene expression levels in
the three primates
Marginal and Interaction Terms
Posterior Inclusion Probability
0.0
H3K4me1
H3K27ac
Pol II
H3K4me3
H3K27me3
0.2
0.5
0.8
H
C
R
1.0
Figure S11. TSS regions associated with inter-species differences
in enriched marks are enriched for differentially expressed (DE)
genes
Fold Enrichment of TSS Associated with
Inter-Species Mark Differences in DE Genes
FDR < 2.5%
FDR < 7.5%
FDR < 10%
H vs C
H3K4me1
H vs R
H3K4me3
H3K27ac
C vs R
H3K27me3
Pol II
Figure S12. An example of mark abundance and gene expression
levels across three species
Rhesus Macaque
Chimpanzee
Human
EENSG00000076043, REX02
RNA
H3K4me1
H3K4me3
H3K27ac
H3K27me3
Pol II
Input
Figure S13. Differences in mark enrichment level plotted against
differences in gene expression level for sliding windows of genes
ordered by increasing differences in expression level
TSS +/- 10 kb
H vs R
C vs R
Scaled Difference in
Enrichment Level
H vs C
Difference in Gene Expression Level
Scaled Difference in
Enrichment Level
TSS +/- 50 kb
Difference in Gene Expression Level
H3K4me1
H3K4me3
H3K27ac
H3K27me3
Pol II
Figure S14. R squared by mark enrichment level differences for
all pairwise comparisons among the three primates
FDR < 2.5%
R2
FDR < 7.5%
FDR < 10%
H vs C
H3K4me1
marginal
H vs R
H3K4me3
H3K27ac
marginal + interactions
C vs R
H3K27me3
Pol II
Predicted Gene Expression Difference
Figure S15. Scatterplot of predicted gene expression level
differences plotted against true gene expression level differences
for DE genes between human and chimpanzee
H3K4me1
True Gene Expression Difference
H3K4me3
H3K27me3
H3K27ac
Pol II
marginal
Difference in Gene Expression Level
Figure S16. Scatterplot of gene expression level differences
plotted against sequence conservation and divergence for DE
H vs C
H vs R
C vs R
genes
Figure S17. R squared by four histone modifications and Pol II or
by four histone modifications alone
B
A
w/o Pol II
R2 in Pol II
R2 in RNA
w/ Pol II
H
C
R
C
H
D
C
R
w/o Pol II
FDR < 5%
R2 in RNA
R2 in Pol II
w/ Pol II
H vs C
H vs R
H3K4me1
marginal
C vs R
H3K4me3
H vs C
H3K27ac
marginal + interactions
H vs R
H3K27me3
C vs R