Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription ( ). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template . Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability . DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Involved in stable X chromosome inactivation . Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (, ). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (, ).
Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism . Able to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap them (By similarity). This prevents PARP1 from further addition of ADP-ribose and thus limits the consumption of nuclear NAD(+), allowing the cell to maintain proper NAD(+) levels in both the nucleus and the mitochondria to promote proper mitochondrial respiration (By similarity). Increases the expression of genes involved in redox metabolism, including SOD3 .
In contrast to isoform 1, does not bind poly-ADP-ribose . Represses SOD3 gene expression .
Subcellular locations: Nucleus, Chromosome
Enriched in inactive X chromosome chromatin and in senescence-associated heterochromatin ( ). Recruited to DNA damage sites in an APLF-dependent manner (, ).
Widely expressed.