Supplementary Table 1 | KATs
Subfamil
y
Locatio
Enzyme
Enzyme
n
activity
Targets
Null phenotype
References
KAT2A
N
A
H3, H4, PGC-1α , α-tubulin
Embryonic lethal
1
KAT2B
N
A
H3, H4, ERRα, ACL, MYOD1
Developmentally normal
2
HAT1
C, N
A
Newly synthesized cytoplasmic histones
Neonatal lethality
3
ATF2
N, M
A
H2B, H4
Neonatal lethality
4
GNAT
H2A, H2B, H3, H4, FXR, PPAR-γ,
p300/
CBP
MYST
SRCs
PEPCK-C, PLAG1, SIRT2, p53, HDAC1,
p300
N, C
A
BCL6, MYOD1
Embryonic lethal
5,6
CBP
N, C
A
H2A, H2B, H3, H4, PPAR-γ, MYOD1
Embryonic lethal
7–9
KAT5
N, C
A
H2A, H4, (H3)
Embryonic lethal
10
KAT6A
N
A
H3, H4, p53
Embryonic or neonatal lethal
11,12
KAT6B
N
A
H3, H4
Partial postnatal lethality
13
KAT7
N
A
H3, H4
Embryonic lethal
14
N, C
A
H3, H4
NCoA1
Obesity, abnormal metabolism
and reproductive system
15,16
NCoA2
Smaller size, abnormal
N, C
A
H3, H4
C, N
A
H3, H4
metabolism
18,19
NCoA3
17
Reduced bodyweight, abnormal
TAFII25
Others
reproductive system
A, P,
0
N
U-A
H3, H4, (H2A), p53
Unknown
20
GTF3Cα
N
A
H2A, H3, H4
Embryonic lethal
21
CLOCK
N, C
A
H3, H4, GR, ARNTL1
Abnormal circadian phase
22,23
All references reported in this table correspond to the first known descriptions and mouse phenotyping studies for each genetic
knockout model. Abbreviations: A, acetylation; ACL, ATP-citrate synthase; ARNTL1, aryl hydrocarbon receptor nuclear translocatorlike protein 1, also known as BMAL1 and MOP3; ATF2, cyclic AMP-dependent transcription factor ATF-2; C, cytosol; CBP, CREBbinding protein; CLOCK, circadian locomoter output cycles protein kaput; ERR-α, steroid hormone receptor ERR1; FXR, bile acid
receptor, also known as farnesoid X-activated receptor; GR, glucocorticoid receptor, also known as NR3C1; GTF3C-α, general
transcription factor 3C polypeptide 1, also known as TFIIIC220; HAT1, histone acetyltransferase type B catalytic subunit; KAT2A,
histone acetyltransferase KAT2A (EC 2.3.1.48), also known as GCN5; KAT2B, histone acetyltransferase KAT2B, also known as PCAF;
KAT5, histone acetyltransferase KAT5, also known as Tip60; KAT6A, histone acetyltransferase KAT6A, also known as MOZ and
MYST3; KAT6B, histone acetyltransferase KAT6B, also known as MORF, MYST4 and MOZ2; KAT7, histone acetyltransferase KAT7,
also known as HBO1 and MYST2; M, mitochondria; MYOD1, myoblast determination protein 1; N, nuclear; NCoA-1, nuclear
receptor coactivator 1, also known as SRC-1; NCoA-2, nuclear receptor coactivator 2, also known as SRC-2; NCoA-3, nuclear
receptor coactivator 3, also known as RAC-3, TRAM1 and AIB1; P, phosphorylation; p53, cellular tumour antigen p53; p300,
histone acetyltransferase p300; PEPCK-C, phosphoenolpyruvate carboxykinase, cytosolic [GTP]; PLAG1, zinc finger protein PLAG1;
PPAR-γ, peroxisome proliferator-activated receptor γ; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1α; SIRT2,
NAD-dependent protein deacetylase sirtuin-2; TAFII250, transcription initiation factor TFIID subunit 1, also known as TAF1 and
p250; α-tubulin, tubulin α-1A chain; U-A, ubiquitin-activating/conjugating.
References:
1.
2.
Xu, W. et al. Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development. Nat. Genet. 26, 229–232 (2000).
Yamauchi, T. et al. Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis. Proc. Natl Acad. Sci.
USA 97, 11303–11306 (2000).
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Nagarajan, P. et al. Histone acetyl transferase 1 is essential for mammalian development, genome stability, and the processing of newly synthesized histones H3 and
H4. PLoS Genet. 9, e1003518 (2013).
Maekawa, T. et al. Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome. J. Biol. Chem. 274, 17813–17819 (1999).
Zheng, G. & Yang, Y.-C. Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2. J. Biol. Chem. 280, 40773–40781 (2005).
Yao, T.P. et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93, 361–372 (1998).
Tanaka, Y. et al. Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein–Taybi syndrome. Proc. Natl Acad. Sci. USA
94, 10215–10220 (1997).
Kung, A.L. et al. Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev. 14, 272–277 (2000).
Zhang, Z., Hofmann, C., Casanova, E., Schütz, G. & Lutz, B. Generation of a conditional allele of the CBP gene in mouse. Genesis 40, 82–89 (2004).
Gorrini, C. et al. Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature 448, 1063–1067 (2007).
Voss, A.K. et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev. Cell 23, 652–663 (2012).
Katsumoto, T. et al. MOZ is essential for maintenance of hematopoietic stem cells. Genes Dev. 20, 1321–1330 (2006).
Thomas, T., Voss, A.K., Chowdhury, K. & Gruss, P. Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development.
Development 127, 2537–2548 (2000).
Kueh, A.J., Dixon, M.P., Voss, A.K. & Thomas, T. HBO1 is required for H3K14 acetylation and normal transcriptional activity during embryonic development. Mol. Cell.
Biol. 31, 845–860 (2011).
Yamada, T. et al. SRC-1 is necessary for skeletal responses to sex hormones in both males and females. J. Bone Miner. Res. 19, 1452–1461 (2004).
Xu, J. et al. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science 279, 1922–1925 (1998).
Gehin, M. et al. The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Mol. Cell. Biol. 22, 5923–5937 (2002).
Liu, Z., Liao, L., Zhou, S. & Xu, J. Generation and validation of a mouse line with a floxed SRC-3/AIB1 allele for conditional knockout. Int. J. Biol. Sci. 4, 202–207
(2008).
Wang, Z. et al. Regulation of somatic growth by the p160 coactivator p/CIP. Proc. Natl Acad. Sci. USA 97, 13549–13554 (2000).
Li, H.-H., Li, A.G., Sheppard, H.M. & Liu, X. Phosphorylation on Thr-55 by TAF1 mediates degradation of p53: a role for TAF1 in cell G1 progression. Mol. Cell 13,
867–878 (2004).
Hsieh, Y.J., Kundu, T.K., Wang, Z., Kovelman, R. & Roeder, R.G. The TFIIIC90 subunit of TFIIIC interacts with multiple components of the RNA polymerase III
machinery and contains a histone-specific acetyltransferase activity. Mol. Cell. Biol. 19, 7697–7704 (1999).
Doi, M., Hirayama, J. & Sassone-Corsi, P. Circadian regulator CLOCK is a histone acetyltransferase. Cell 125, 497–508 (2006).
Debruyne, J.P. et al. A clock shock: mouse CLOCK is not required for circadian oscillator function. Neuron 50, 465–477 (2006).