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Core histone macro-H2A.1 AlphaSync

Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription^1,2,3. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template⁴. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability⁵. 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 inactivation⁶. Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes^7,8. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin^9,10. Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism¹¹. 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 SOD3¹². In contrast to isoform 1, does not bind poly-ADP-ribose¹³. Represses SOD3 gene expression¹⁴.

AlphaFold DB , UniProt , Accession O75367, Species HUMAN (Homo sapiens, Human), Gene MACROH2A1, Length 369 aa.