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E-GEOD-56307 - Histone chaperone HIRA orchestrates H4K16ac-decorated dynamic chromatin in senescent cells and is required for suppression of oncogene-induced neoplasia

Status
Released on 26 November 2014, last updated on 23 December 2014
Organism
Homo sapiens
Samples (22)
Protocols (4)
Description
Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Histone chaperone HIRA deposits nucleosome-destabilizing histone variant H3.3 into chromatin in a DNA replication-independent manner. Histone H3.3 and a subset of other typically “replication-dependent” core histones were expressed in non-proliferating senescent cells, the latter linked to alternative mRNA splicing and polyadenylation. Senescent cells incorporated newly-synthesized histones into chromatin, partially dependent on HIRA. HIRA and newly-deposited histone H3.3 co-localized at promoters of expressed genes, and their distribution shifted between proliferating and senescent cells, paralleling changes in gene expression. In senescent cells, gene promoters showed exceptional enrichment of a histone acetylation linked to open and dynamic chromatin, H4K16ac. Abundance of H4K16ac depended on HIRA. In the mouse, inactivation of HIRA downregulated H4K16ac and dramatically enhanced oncogene-induced hyperplasia. To conclude, HIRA controls a previously undefined dynamic non-canonical H4K16ac-decorated chromatin landscape in senescence, and also plays an unanticipated role in suppression of oncogene-induced neoplasia. Examination of HIRA protein binding alongside histone modification H4K16ac and H3.3 in proliferating and senescent IMR90 cells
Experiment type
ChIP-seq 
Contacts
Peter Adams <geo@ncbi.nlm.nih.gov>, John J Cole, Peter D Adams, Taranjit S Rai
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
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