HIRA: a histone chaperone. Necessary to mediate DNA-synthesis-independent nucleosome assembly. Interacts with UBN1, CABIN, and ASF1A in the cell nucleus to form the evolutionarily conserved HUCA histone chaperone complex that deposits the variant histone H3.3 into chromatin in a DNA-replication independent manner. Required for deposition of histone H3.3 at the transcription start sites of genes, where incorporation of histone H3.3 facilitates nucleosome destabilization and contributes to transcriptional activation. Histone H3.3 is also linked to gene silencing and is incorporated into regions of the genome thought to be transcriptionally inactive. While some incorporation of H3.3 into heterochromatin is facilitated by an additional histone chaperone complex containing ATRX and DAXX (ie. telomeric incorporation of H3.3), HIRA is required for incorporation of histone H3.3 and formation of senescence-associated heterochromatin foci (SAHF) during cellular senescence. HIRA is ubiquitously expressed during mouse embryonic development. In the adult mouse, HIRA is expressed at high levels in the kidney, skeletal muscle, and pancreas, but it is expressed at lower levels in the heart, lung, placenta, brain, and liver. A missing copy of the HIRA gene on human chromosome region 22q11.2 is a common characteristic of DiGeorge syndrome patients and insufficient production of the HIRA protein may disrupt normal embryonic development. Two isoforms of the human protein result from alternative splicing.
Protein type: Cell development/differentiation; Transcription regulation; Cell cycle regulation
Chromosomal Location of Human Ortholog: 22q11.21
Cellular Component: nucleoplasm; PML body; protein complex; nuclear chromatin; nucleus
Molecular Function: protein binding; chromatin binding; transcription corepressor activity; transcription factor activity
Biological Process: osteoblast differentiation; regulation of transcription from RNA polymerase II promoter; anatomical structure morphogenesis; muscle cell differentiation; transcription, DNA-dependent; DNA replication-independent nucleosome assembly; gastrulation; chromatin modification
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