Disease relevance of H2AFY

• These results show the power of combined array CGH and SAGE analysis for the identification of candidate amplicon targets and identify H2AFJ and EPS8 as novel putative oncogenes in breast cancer [1].

High impact information on H2AFY

• We further demonstrate that MACROH2A1 deposition is regulated by the CULLIN3/SPOP ligase complex and is actively involved in stable X inactivation, likely through the formation of an additional layer of epigenetic silencing [2].
• Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase [2].
• Importantly, RNAi-mediated knock-down of CULLIN3 or SPOP results in loss of MACROH2A1 from the inactivated X chromosome (Xi), leading to reactivation of the Xi in the presence of inhibitors of DNA methylation and histone deacetylation [2].
• H4 hypoacetylation, macroH2A1.2 incorporation, and DNA methylation all occur subsequently [3].
• The amino acid sequence of human MACROH2A2 is 68% identical to human MACROH2A1 [4].

Biological context of H2AFY

• Mutually exclusive exon use in the gene H2AFY produces macroH2A1.2, whose tissue distribution differs [5].
• These results provide the first direct evidence that multiple post-translational modifications are imposed on macroH2A1.2, suggesting that, like canonical H2A, this variant H2A is subject to regulation by combinatorial use of covalent modifications [6].

Anatomical context of H2AFY

• We show here that a small population of macroH2A1.2 is mono-ubiquitinated in human HeLa cells [7].
• The amplification of all four candidates was confirmed by quantitative PCR and fluorescence in situ hybridization, but only H2AFJ and EPS8 were overexpressed in breast tumors with 12p13 amplification compared with a panel of normal mammary epithelial cells [1].

Analytical, diagnostic and therapeutic context of H2AFY

• Northern blot analysis showed that the macroH2A1.1 and macroH2A1.2 subtypes were expressed as mRNA species with a size of 1.5 and 4.4 kb, respectively [8].

References