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©The Author(s) 2024.
World J Hepatol. May 27, 2024; 16(5): 703-715
Published online May 27, 2024. doi: 10.4254/wjh.v16.i5.703
Published online May 27, 2024. doi: 10.4254/wjh.v16.i5.703
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] |
Table 2 Effect of histone methylation on inflammatory injury
Histone methylation | HMTs/HDMs | Mechanisms | Effects on Inflammatory Injury | Ref. |
H3K4me3↑ | SET7/9/KMT7 | (+) SET7/9→promoter (TNF-α→Pro-inflammatory genes) ←NF-κB p65 | Inflammatory reaction↑ | [58] |
H3K79me1/2/3↑ | DOT1L | (+) DOT1L→Pathways of SREBP→ (-) Inflammatory expression of macrophages | Inflammatory reaction↓ | [49] |
H3R2me3↑ | PRMT5 | (+) PRMT5→promoter (OXR1A) →Growth Hormone | Oxidation stress↑ | [64,65] |
H3K27me3↓ | JMJD3/KDM6B | In case of non-diabetic injury: (+) IFN-β→JAK1/3-STAT3→JMJD3→STING-TBK1/IRF3/IFN-α | In case of non-diabetic injury:Wound Recovery | [59-63] |
In case of diabetic injury: (-) IL-6→JAK1/3-STAT3→JMJD3→IFN-α; (+) IL-6→JAK1/3-STAT3→JMJD3→NF-κB | In case of diabetic injury:Inflammatory reaction↑ |
Table 3 Effect of histone methylation on hepatic fibrosis
Histone methylation | Functions | Effects on fibrosis | Ref. |
H3K9me1/2/3↑ | (Upstream) (-) Transcription initiation | Expression of PPARγ↓ | [67,69,70] |
Hepatic Fibrosis↑ | |||
H3K27me1/2/3↑ | (Downstream) (-) Transcriptional extensions | Expression of PPARγ↓ | [67,69,70] |
Hepatic Fibrosis↑ | |||
H3K4me2/3↑ | (The whole process) (+) Genes for fibrosis (TGF-β1, TIMP-1, α-SMA and Collagen type I) | Hepatic Fibrosis↑ | [67,69,70] |
H3K36me3↑ |
Table 4 Effect of histone methylation on carcinogenesis of fatty liver
Histone methylation | HMTs/HDMs | Functions | Effects on HCC | Ref. |
H3K4me2↑ | SETD7/KMT7 | (+) Cell cycle G1 phase → S phase | ↑ | [72,73] |
H3K9me1/2↑ | G9a/KMT1C | (-) Expression of oncogenic factor RARRES3 and pro-apoptotic gene Bcl-G | ↑ | [85,86] |
H3K9me3↑ | SUV39H1/KMT1A | (+) Cell cycle G1 phase → S phase | ↑ | [87,88] |
H3K27me3↑ | EZH2/KMT6A | (+) Wnt/β-linked protein signaling pathways | ↑ | [91,92] |
H4K20me1↑ | SET8/KMT5A | (+) Cell cycle G1 phase → S phase | ↑ | [94,95] |
H3K4me1/2/3↓ | JARID1B/KDM5B | (+) Cell cycle G1 phase → S phase | ↑ | [75] |
(-) Oncogenic expression ← transcription factors (E2F1, P15 and P27) | ||||
H3K4me1/2↓ | LSD1/LSD2/KDM1A | (+) Cell cycle G1 phase → S phase | ↑ | [77-79,90] |
H3K9 me1/2↓ | (-) H3K4me1/2↓→Inhibitor expression (β-linked protein signaling) | |||
(+) β-linked protein +TCF/LEF→Target gene expression (Oncogenic) | ||||
H3K9me1/2↓ | JMJD1A/KDM3A | (+) PI3K/AP-1 pathway | ↑ | [89,90] |
(+) JAK2-STAT3 signaling pathways | ||||
(+) Wnt/β-linked protein signaling pathways |
- Citation: Xu L, Fan YH, Zhang XJ, Bai L. Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease. World J Hepatol 2024; 16(5): 703-715
- URL: https://www.wjgnet.com/1948-5182/full/v16/i5/703.htm
- DOI: https://dx.doi.org/10.4254/wjh.v16.i5.703