core histone macro-H2A.1; histone macroH2A1; medulloblastoma antigen MU-MB-50.205 (H2AFY, MACROH2A1, mH2A1, H2A.y, H2A/y)
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Function
- variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription
- involved in stable X chromosome inactivation.
- inhibits binding of transcription factors & interferes with activity of remodelling SWI/SNF complexes
- inhibits histone acetylation by EP300 & recruits class 1 HDACs, which induces an hypoacetylated state of chromatin
- isoform 1 but not isoform 2, binds ADP-ribose & O-acetyl-ADP-ribose, & may be involved in ADP-ribose-mediated chromatin modulation
- interacts with SPOP
- part of a complex consisting of H2AFY, CUL3 & SPOP
- interacts with HDAC1 & HDAC2
- monoubiquitinated at either Lys-116 or Lys-117
- may also be polyubiquitinated
- ubiquitination is mediated by the CUL3/SPOP E3 complex &
- does not promote proteasomal degradation
- instead, required for enrichment in inactive X chromosome chromatin
Structure
- contains 1 histone H2A domain
- contains 1 Macro domain
Compartment
- nucleus
- enriched in inactive X chromosome chromatin & in senescence-associated heterochromatin
Alternative splicing
named isoforms=2 Note=Specifically binds ADP-ribose and O-acetyl-ADP-ribose Important residues for binding are Asp-203, Gly-224, Gly-314 and Phe-348
Expression
Pathology
- number of individuals with antibodies against H2AFY is 2-fold higher in pediatric patients with cancer compared to healthy controls