MACROH2A1

Isoform 1

The macro domain specifically binds poly-ADP-ribose.

Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (PubMed:12718888, PubMed:15621527, PubMed:16428466). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template (PubMed:15897469). Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (PubMed:15897469). 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 (PubMed:15897469). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (PubMed:12718888, PubMed:16428466). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16107708, PubMed:16428466).

Isoform 1

Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism (PubMed:15902274). 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 (PubMed:23022728).

Isoform 2

In contrast to isoform 1, does not bind poly-ADP-ribose (PubMed:15902274). Represses SOD3 gene expression (PubMed:23022728).

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.

Belongs to the histone H2A family.

Widely expressed.

• Nucleus
• Chromosome
• Enriched in inactive X chromosome chromatin and in senescence-associated heterochromatin (PubMed:15621527, PubMed:15897469, PubMed:9634239). Recruited to DNA damage sites in an APLF-dependent manner (PubMed:21211722, PubMed:29905837).

H2AFY, MACROH2A1, Core histone macro-H2A.1, Histone macroH2A1, mH2A1, Histone H2A.y, Medulloblastoma antigen MU-MB-50.205, H2A/y

• entrezGene:9555
• omim:610054
• swissprot:O75367

Proteins

Immunology & Infectious Disease

39617Da