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Figure 1. Epigenetic and epitranscriptomic regulation in MASLD pathogenesis. Epigenetic regulators SNAIL1 recruits HDAC1/2 to catalyze repressive deacetylation of H3K9 and H3K27 on the promoter region of lipogenic genes, thereby suppressing lipogenesis, while SLUG interacts with LSD1 that can demethylate H3K9, thus increasing lipogenic gene transcription in an opposite way. Both SNAIL1 and SLUG can recruit P300, which stimulates H3K27 acetylation, promoting cell-cycle gene expression in response to liver injury. Epitranscriptomic regulation, especially m⁶A modification, involves writers, erasers, and readers. These m⁶A regulators modulate liver metabolism by altering the RNA methylation of genes involved in lipogenesis, fatty acid oxidation, inflammation, and fibrogenic pathways, controlling different stages of MASLD progression by affecting the RNA fate. Epigenetic mechanisms can influence epitranscriptomic modifications, while epitranscriptomic processes can, in turn, modulate epigenetic states, creating a dynamic interplay that mutually shapes each other’s regulatory roles in the MASLD liver. This figure is created in BioRender. Zheng Q. (2024) https://BioRender.com/w13h393. Me: Methylation; Ac: acetylation; m⁶A: N⁶-methyladenosine; FTO: fat mass and obesity-associated protein; METTL3: methyltransferase-like 3; METTL14: methyltransferase-like 14; MASLD: metabolic dysfunction-associated steatotic liver disease; LSD1: lysine-specific demethylase-1; HDAC1/2: histone deacetylase 1/2; H3K9: histone H3 lysine-9; H3K27: histone H3 lysine-27; WTAP: wilms tumor 1-associated protein; YTHDC1/2: YTH domain-containing protein 1/2; YTHDF1/2/3: YTH domain-containing family protein 1/2/3.