Supplementary Table 2 | KDACs
Subfamil
y
Locatio
Enzyme
Enzyme
n
activity
HDAC1
N,C
DA
HDAC2
N
DA
HDAC3
N
DA
Targets
Null phenotype
References
E2F1, STAT3
Embryonic lethal
1,2
H2A, H2B, H3, H4, GR, YY1, BCL-6,
Neonatal lethality,
STAT3
smaller size
1–3
Embryonic lethal
4,5
H2A, H2B, H3, H4, AR, SHP, p53, MYOD1,
I
H2A, H2B, H3, H4, SHP, YY1, Eryf1, p65,
STAT3, MEF2D
Partial neonatal
HDAC8
N, C
DA
H2A, H2B, H3, H4, SMC-3, ERRα
lethality
6–8
Postnatal lethality,
HDAC4
N, C
DA
H2A, H2B, H3, H4, GCM1, Eryf1, HP1-β
N, C,
IIA
smaller size
8
Cardiac
HDAC5
GA
DA
H2A, H2B, H3, H4, GCM1, SMAD7, HP1-β
hypertrophy
9
HDAC7
N, C, M
DA
H2A, H2B, H3, H4, PLAG1
Embryonic lethal
10,11
HDAC9
N, C
DA
H2A, H2B, H3, H4
Cardiac
hypertrophy
12
Higher body
weight, abnormal
IIB
HDAC6
H2A, H2B, H3, H4, α-tubulin , HSP90,
immune and
C, N
DA
SHP, SMAD7
skeletal system
13
C
DA
H2A, H2B, H3, H4
Unknown
14
HDAC1
0
H2A, H3, H4, PGC-1-α , PPAR-γ, FOXO1,
SIRT1
SIRT2
SIRT3
III
N, C
C
M
DA, DC
DA, DC
DA, DC
FOXO3, CRTC2, AceCS, p53, NOTCH1, p65,
Developmental
HIF-1α, LXRβ, FXR
defects
H3, H4, ACL, α-tubulin, PEPCK-C, FOXO1,
Developmentally
p65
normal
LCAD, HMGCS2, GDH1, SOD, IDH-2,
Developmentally
OXPHOS, AceCS2
normal
18,23,24
Developmentally
25–27
ADPR,
SIRT4
M
L, B
GDH1, MCD, PDC
15–18
18–22
normal
DA,
DM,
SIRT5
M, C, N
DS, DG
Developmentally
CPS1
normal
28–30
H3, IGF-1, HIF-1α, KAT2A, p65
Premature aging
31–33
DA,
ADPR,
SIRT6
N
D
Smaller size, short
lifespan, heart
IV
SIRT7
N
HDAC1
N, C,
1
PM
DA
H3, GABPB-1, p53, SMAD6
defects
34,35
Developmentally
DA
H2A, H2B, H3, H4
normal
36
All references reported in this table correspond to the first known descriptions and mouse phenotyping studies for each genetic knockout
model. Abbreviations: AceCS1, acetyl-coenzyme A synthetase, cytoplasmic, also known as ACSS2; AceCS2, acetyl-coenzyme A
synthetase 2-like, mitochondrial; ADPR, ADP-ribosylation; B, biotinylation; BCL-6, B-cell lymphoma 6 protein; C, cytosol; CPS1,
carbamoyl-phosphate synthase [ammonia], mitochondrial; CRTC2, CREB-regulated transcription coactivator 2; D, deacylation; DA,
deacetylation; DC, decrotonylation; DM, demalonylation; DS, desuccinylation; DG, deglutaryation; E2F1, transcription factor E2F1;
ERRα, steroid hormone receptor ERR1, also known as ESRRA; Eryf1, erythroid transcription factor, also known as GATA1; FOXO1,
forkhead box protein O1; FOXO3, forkhead box protein O3; FXR, bile acid receptor, also known as farnesoid X-activated receptor; GA,
golgi apparatus; GABPB-1, GA-binding protein subunit β1; GCM1, chorion-specific transcription factor GCMa; GDH1, glutamate
dehydrogenase 1, mitochondrial (GDH 1); GR, glucocorticoid receptor, also known as NR3C1; HDAC1-11, histone deacetylase 1-11;
HIF-1α, hypoxia-inducible factor 1α; HMGCS2, hydroxymethylglutaryl-CoA synthase, mitochondrial (HMG-CoA synthase); HP1-β,
chromobox protein homolog 1; IDH-2, isocitrate dehydrogenase [NAD] regulatory subunit 2, mitochondrial; IGF-1 insulin-like growth
factor I; L, lipoylation; LCAD, long-chain specific acyl-CoA dehydrogenase, mitochondrial; LXRβ, oxysterols receptor LXR-β; M,
mitochondria; MCD, malonyl-CoA decarboxylase, mitochondrial (MCD); MEF2D, myocyte-specific enhancer factor 2D; MYOD1,
myoblast determination protein 1; N, nuclear; NOTCH1, neurogenic locus notch homolog protein 1; p53, cellular tumour antigen p53;
p65, transcription factor p65; PDC, pyruvate dehydrogenase complex; PEPCK-C, phosphoenolpyruvate carboxykinase, cytosolic [GTP];
PLAG1, zinc finger protein PLAG1; PM, plasma membrane;. SHP, Nuclear receptor subfamily 0 group B member 2; SIRT1-7, NADdependent protein deacetylase sirtuin-1-7; SMAD7, mothers against decapentaplegic homolog 7; SMC-3, structural maintenance of
chromosomes protein 3; SOD, superoxide dismutase; STAT3, signal transducer and activator of transcription 3; α-tubulin, tubulin α1A
chain; YY1, transcriptional repressor protein YY1, also known as EF-E1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
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