Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

Table 1 Effect of histone methylation on glycolipid metabolism

Histone methylation	HMTs/HDMs	Mechanisms	Effects on glycolipid metabolism	Ref.
H3K4me3↑	MLL2/KMT2B	-	Regulation of glucose homeostasis	[20]
H3K4me3↑	MLL3/KMT2C	(+) KMT2C (2D) + PTIP→promoter (PPARγ) ←Transcript (C/EBPα); (+) KMT2C (2D) + PTIP→promoters (LPL, SREBF2, SCD1) ←Transcript (E2F1)	Lipid synthesis↑	[21,23,68]
	MLL4/KMT2D
H3K9me2/3↑	SUV39H1/KMT1A	(-) KMT1A (1D) →Transcript (C/EBPα) ←Enhancer (AP-2α); (-) KMT1D + PRDM16→promoter (HSD11B1)	Lipid synthesis↓	[27,28]
	EHMT1/KMT1D		Blood glucose↑
H3K9me2/3↑	EHMT2/KMT1C	(-) KMT1C→promoter (PPARγ) ←Transcript (C/EBPα); (+) KMT1C→Expression of HMGA1	Lipid synthesis↓	[30,31]
			Impaired insulin signal↓
H3K27me3↑	EZH2/KMT6A	(-) KMT6A→promoter (Mogat1) →MAG→DAG	Lipid synthesis↑	[42,45]
H3K79me1/2/↑	DOT1L	(+) DOT1L→Pathways of SREBP	Lipid synthesis↑	[49]
		(+) DOT1L→Brown and beige fat production and thermogenesis
H3K4me1/2↓	LSD1/KDM1A	(-) KDM1A + PRDM16→promoter (HSD11B1)	Lipid synthesis↑	[24,25]
			Blood glucose↓
H3K9me2/me3↓	JMJD2B/KDM4B	(+) KDM4B + PTIP→promoter (PPARγ) ←Transcript (C/EBPα)	Lipid synthesis↑	[32,33]
		(+) KDM4B + LXRα
H3k9me3↓	JMJD1C/KDM3C	(+) KDM3C + USF1→promoter; (Lipogenesis genes)	Lipid synthesis↑	[34]
H3K9me1/2↓	JHDM2a/KDM3A	(+) KDM3A (β-adrenaline) →PPRE←promoter (PPARγ + RXRα)	Lipid synthesis↓	[35,36]
H3K9me2↓	JHDM1D/KDM7A	(+) KDM7A→promoter (DGAT2)	Lipid synthesis↑	[37]
H3K27me2↓
H3K27me3↓	JMJD3/KDM6B	(+) KDM6B + islet1→promoter (SNAI1)	Lipid synthesis↓	[46]
H3K27me3↓	-	(+) promoter (LepRb) →slug-Epigenetic reediting-Leptin resistance axis	Leptin resistance↑	[48]
H3K36me2↑	NSD2	(-) NSD2→promoter (PPARγ)	Lipid synthesis↓	[47]
H3K27me3↓
H3K9me2/3↓	Phf2	(+) Phf2→ChREBP→promoter (FASN)	Lipid synthesis↑	[39,40]
			Fructose decomposition↑
H4K20me1↓	KDM7B	(-) promoter (RNA Pol II) →H4K20me1→Expression of glycolytic genes	Lipid synthesis↑	[55]
H4K20me3↓	-	(+) ChREBP→ChoRE + promoter (FASN) →H4K20me3→Expression of FASN	Lipid synthesis↑	[53]

HMTs: Histone methyltransferases; HDMs: Histone demethylases; Mogat1: Monoacylglycerol O-acyltransferase 1; DAG: Diacylglycerol; FASN: Fatty acid synthase; E2F1: E2F transcription factor 1; PTIP: Pax trans-activating structural domain-interacted protein; PPRE: The PPAR response element; Phf2: Plant homologous structural domain finger 2.