Alcohol-induced protein hyperacetylation: Mechanisms and consequences

Table 1 Ethanol-induced hyperacetylated proteins

Protein	EtOH exposure	System	References
Histone H3	Acute and chronic	Hepatocytes, rat liver, stellate cells	[817–21]
p53	Chronic	Rat liver, VLA17 cells	[61]
PGC-1α	Chronic	Rat liver, mouse liver	[1214]
SREPB-1c	Chronic	H4IIEC3 cells	[12]
α-tubulin	Chronic	WIF-B cells, rat liver	[113975]
AceCS2	Chronic	Rat Liver	[13]

Table 2 Newly identified ethanol-induced hyperacetylated proteins

Liver subcellularlocation1	EtOH exposure	Function	No. proteinsidentified
Cytosol	Chronic	AA metabolism	7
		Carbohydrate metabolism	4
		Other metabolic pathways	3
		Oxidative stress	3
		Other	2
Mitochondria	Chronic	Lipid metabolism	12
		AA metabolism	5
		Oxidative phosphorylation	2

¹Our unpublished results.

Table 3 Deacetylases expressed in the liver

Class	Enzyme	In liver? (methods)	Location	Substrates
I	HDAC1	Yes (RT-PCR, IB, IHC, activity)	Nucleus	Histones, p53, retinoblastoma, STAT3, androgen receptor, estrogen receptor, Smad7, other transcription factors
	HDAC2	Yes (RT-PCR)	Nucleus	Histones, STAT3, other transcription factors
	HDAC3	Yes (RT-PCR, IB, activity)	Nucleus	Histones, STAT3, Smad7, other transcription factors
	HDAC8	Yes (RT-PCR)	Nucleus Cytoplasm	Histones, transcription factors, smooth muscle actin
II	HDAC4	Yes/No (RT-PCR)	Nucleus Cytoplasm	Transcription factors
	HDAC5	Yes (RT-PCR)	Nucleus Cytoplasm	Transcription factors
	HDAC6	Yes (RT-PCR, IB, IF)	Cytoplasm	Tubulin, cortactin, HSP90
	HDAC7	No	Nucleus Cytoplasm	HIFα, other transcription factors
	HDAC9	No	Nucleus Cytoplasm	Transcription factors
	HDAC10	Yes (RT-PCR)	Nucleus Cytoplasm	Phosphatase pp1
III	SirT1	Yes (RT-PCR, IB)	Nucleus	Histones, PGC-1α, LXR, p53, other transcription factors
	SirT2	Yes/No (RT-PCR, IB)	Cytoplasm	Histone H4, tubulin
	SirT3	Yes (RT-PCR, IB)	Mitochondria	Acetyl CoA synthetase 2, glutamine dehydrogenase, ICDH2
	SirT4	Yes (RT-PCR)	Mitochondria	Glutamine dehydrogenase
	SirT5	Yes (RT-PCR)	Mitochondria	Cytochrome c
	SirT6	Yes (RT-PCR)	Nucleus	DNA polymerase β
	SirT7	Yes (RT-PCR)	Nucleus	RNA polymerase I
IV	HDAC11	Unknown	Nucleus	Unknown

IB: Immunoblotting; IHC: Immunohistochemistry; IF: Immunofluorescence; HIFα: Hypoxia-inducible factor α; LXR: Liver x receptor; ICHD2: Isocitrate dehydrogenase.

Table 4 Histone acetyltransferases expressed in the liver

Family	HAT	In liver? (methods)	Location	Substrates	References
Gcn5/PCAF	PCAF	Yes (IB)	Nucleus Cytoplasm	Histones, p53, PGC-1a, other transcription factors, cortactin	[52–58]
p300/CBP	CBP	Yes (IB)	Nucleus	Histones, E1A, p53, SRC-1, TIF2, ACTR, SREBP, other transcription factors	[545758]
	p300	Yes (IB)	Nucleus	Histones, E1A, p53, SRC-1,TIF2, TAT, ACTR, SREBP, other transcription factors	[1854555758]
MYST	TIP60	Yes (IB)	Nucleus Cytoplasm	Histones H3 and H4, androgen receptor	[5457]
	HBO	Unknown	Nucleus	Histones H3 and H4	[5758]
	MOZ	No	Nucleus	Histones H3 and H4	[100]
	MORF	Yes (RT-PCR)	Nucleus	Histones H3 and H4	[101102]

E1A: Adenovirus early region 1A; SRC-1: Steroid receptor coactivator; TIF2: Transcriptional intermediary factor 2.