Table 2.

Examples of histone modifications and their association with aberrant gene expression in nonalcoholic fatty liver disease.

Gene	Stage	Association between Epigenetic Determinant and Gene Expression	References
SREBP1c, FASN ACLYS, Pparγ	NAFLD	Blocking the hyperacetylation of lysine 9 and 36 at histone 3 (H3K9 and H3K36) in the promoter of lipogenesis-related genes (SREBP1c, FASN, ACLYS, Pparγ) prevented NAFLD	[100]
Pparα	NAFLDSteatosis	Hepatic lipid accumulation induced aberrant H3K9me3 and H3K4me3 status in Pparα gene and other hepatic lipid catabolism network genes, which may contribute to hepatic steatosis and the pathogenesis of NAFLD	[102]
ChREBP	Hepatic Steatosis	p300 associates and regulates carbohydrate-responsive element–binding protein (ChREBP) transcriptional activity by acetylation. Inhibition of hepatic p300 activity may be beneficial for treating hepatic steatosis	[103]
Pparγ2	Hepatic steatosis	Histone H3 lysine 4 (H3K4) methyltransferase MLL4/KMT2D directs overnutrition-induced murine steatosis via its coactivator function for PPARγ2	[104]
Pparγ2, CD36, FABP4, PLIN2, CIDEC,	Hepatic steatosis	Overexpressing JMJD2B upregulated Pparγ2 expression which lead to a concomitant increase in its steatosis target genes by removing repressive histone marks H3K9me2 and H3K9me3 near LXREs of lipogenic gene promoters leading to the development of NAFLD	[105]

ACLY, ATP-citrate lyase; CD36, fatty acid translocase; ChREBP, carbohydrate-responsive element–binding protein; FABP4, fatty acid-binding protein 4; FASN, fatty acid synthase; HFD, high-fat diet; JMJD2B, jumonji domain-containing protein 2B histone demethylase; LXRα, liver X receptor α; NAFLD, nonalcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; p300, transcriptional coactivator with histone acetylase activity; PPARγ, peroxisome proliferator-activated receptor gamma; SIRT1, Sirtuin type 1;SREBP-1c, sterol regulatory element-binding protein 1c.