HIRA

This gene encodes a histone chaperone that preferentially places the variant histone H3.3 in nucleosomes. Orthologs of this gene in yeast, flies, and plants are necessary for the formation of transcriptionally silent heterochomatin. This gene plays an important role in the formation of the senescence-associated heterochromatin foci. These foci likely mediate the irreversible cell cycle changes that occur in senescent cells. It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development. [provided by RefSeq, Jul 2008]

Full Name

Histone Cell Cycle Regulator

Function

Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit.

Biological Process

Anatomical structure morphogenesis Source: ProtInc
DNA replication-independent chromatin assembly Source: UniProtKB
Gastrulation Source: Ensembl
Muscle cell differentiation Source: Ensembl
Osteoblast differentiation Source: Ensembl
Regulation of transcription by RNA polymerase II Source: ProtInc
Transcription, DNA-templated Source: InterPro

Cellular Location

Nucleus; PML body. Primarily, though not exclusively, localized to the nucleus. Localizes to PML bodies immediately prior to onset of senescence.

PTM

Sumoylated.
Phosphorylated by CDK2/CCNA1 and CDK2/CCNE1 on Thr-555 in vitro. Also phosphorylated on Thr-555 and Ser-687 in vivo.