Molecular dynamics of the most studied histone post-translational modifications (HPTMs) in hepatocellular carcinoma (HCC). (IMAGE)
Caption
Key modifications involved in HCC include lysine methylation and acetylation, regulated by KMTs/KDMs and HATs/HDACs, respectively, which influence chromatin accessibility and transcriptional activity. Additional PTMs, such as arginine methylation by PRMTs, phosphorylation by kinases, citrullination by PADs and ADP-ribosylation by PARPs also contribute to epigenetic remodelling. Some of these modifications, such as acetylation, citrullination, phosphorylation and ADP-ribosylation, alter the charge of the targeted amino acid residues, thereby affecting histone-DNA interactions and chromatin compaction. In contrast, methylation does not change the residue’s charge but can still influence chromatin structure by serving as docking sites for regulatory proteins. Ac, acetylation; Ac-CoA, acetyl-coenzyme A; ADPr, ADP-ribose; α-KG, α-ketoglutarate; BER, base excision repair; Cit, citrullination; CoA, coenzyme A; HATs, histone acetyltransferases; HDACs, histone deacetylases; JmjC, Jumonji C domain-containing demethylases; KDMs, lysine demethylases; KMTs, lysine methyltransferases; MARylation, mono-ADP-ribosylation; Me, methylation; PADs, peptidyl arginine deiminases; PARPs, poly(ADP-ribose) polymerases; PARylation, poly-ADP-ribosylation; Ph, phosphorylation; PRMTs, protein arginine methyltransferases; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; Succ., succinate.
Credit
By Barbara Bueloni, Maite Garcia Fernandez de Barrena, Matias Antonio Avila, Juan Bayo, Guillermo Mazzolini
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CC BY-NC