FUNCTION: 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 and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces an hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation.
SUBUNIT STRUCTURE: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. Interacts with SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Interacts with HDAC1 and HDAC2 (By similarity).
SUBCELLULAR LOCATION: Nucleus. Chromosome. Note: Enriched in inactive X chromosome chromatin and in senescence-associated heterochromatin. In quiescent lymphocytes, associated with centromeric constitutive heterochromatin.
TISSUE SPECIFICTY: Ubiquitously expressed, with high levels in testis. Present in liver, kidney and adrenal gland (at protein level). In the liver, present in hepatocytes and at a lesser extent in cells of the bile ducts. In the kidney, present in proximal and distal convoluted tubules and in straight proximal tubules. In the adrenal gland, present in inner cells of the cortex and medulla.
PTM: Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin (By similarity).
SEQUENCE SIMILARITIES: Contains 1 histone H2A domain.
Contains 1 Macro domain.