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HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia #MMPMID25512559
Rai TS; Cole JJ; Nelson DM; Dikovskaya D; Faller WJ; Vizioli MG; Hewitt RN; Anannya O; McBryan T; Manoharan I; van Tuyn J; Morrice N; Pchelintsev NA; Ivanov A; Brock C; Drotar ME; Nixon C; Clark W; Sansom OJ; Anderson KI; King A; Blyth K; Adams PD
Genes Dev 2014[Dec]; 28 (24): 2712-25 PMID25512559show ga
Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Rai et al. show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape, and this depends on HIRA. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia.