{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n H2AC11 is a replication‐dependent core histone belonging to the H2A family that plays a critical role in the packaging of DNA into nucleosomes and the regulation of gene expression. As a structural component of chromatin, H2AC11 contributes to the formation of higher‐order chromatin architecture, thereby influencing genomic accessibility, transcriptional programs, and ultimately cell cycle progression. In normal cells the tight regulation and proper 3′ end processing of replication‐dependent histone mRNAs—including those encoding H2A variants—is essential for cell proliferation and maintenance of genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Alterations in the expression and regulation of histone genes, such as aberrant up‐regulation or dysregulated post‐translational modifications, have been implicated in various human malignancies. Gene‐set analyses have uncovered that changes in clustered histone gene expression correlate with disruptions in DNA replication and repair pathways in cancers, and elevated expression of histone family members is associated with poorer clinical outcomes in tumors including cervical cancer and glioma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, emerging evidence indicates that metabolic cues, such as those mediated by pyruvate, can repress histone gene expression to induce chromatin decompaction and alter gene regulation, thereby modulating cancer cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Together, these studies suggest that H2AC11, like other replication‐dependent H2A variants, is not only fundamental for nucleosome assembly and chromatin structure but also serves as an important molecular link between epigenetic regulation and cellular responses to genotoxic and metabolic stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ilaria Pettinati, Pawel Grzechnik, Claudia Ribeiro de Almeida, et al. 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