Core histone macro-H2A.2 (MACROH2A2)

MacroH2A.2 is a member of the histone H2A family encoded by the MACROH2A2 gene (H2AFY2), distinguished by its tripartite structure: a histone fold, an intrinsically disordered linker, and a unique globular macrodomain[4]. It integrates into nucleosomes in place of conventional H2A, reducing transcription and contributing to stable gene silencing, including X chromosome inactivation[2]. MacroH2A variants—including MacroH2A.2—are essential for maintaining higher-order chromatin architecture, stabilizing differentiated cellular states, and suppressing transcriptional noise[3][4]. Unlike its paralog macroH2A1.1, which binds to ADP-ribose and can regulate PARP-1 activity, MacroH2A.2’s macrodomain is incompatible with nucleotide binding and does not directly interact with cellular metabolites[1]. Dysregulation of macroH2A histone variants has context-dependent effects in cancer, often acting as tumor suppressors or barriers to cellular reprogramming[4].

Other names

MacroH2A.2 histoneMACROH2A2H2AFY2Histone macroH2A2mH2A2core histone macro-H2A.2H2A histone family member Y2core histone macroH2A2.2

Not applicable. No drugs are known to act directly on MacroH2A.2.