H2A.Z is a histone H2A variant that is essential for viability in organisms such as Tetrahymena, Drosophila and mice. In S. cerevisiae, loss of H2A.Z is tolerated, but proper regulation of gene expression is affected. Genetics and genome wide localization studies show that yeast H2A.Z physically localizes to the promoters of genes and functions in part to protect active genes in euchromatin from being silenced by heterochromatin spreading. To date, the function of H2A.Z in mammalian cells is less clear and evidence so far suggests that it has a role in chromatin compaction and heterochromatin silencing. In this study, we found that the bulk of H2A.Z is excluded from constitutive heterochromatin in differentiated human and mouse cells. Consistent with this observation, analyses of H2A.Z- or H2A-containing mono-nucleosomes show that the H3 associated with H2A.Z has lower levels of K9-methylation but higher levels of K4-methylation compared to those associated with H2A. We also found that a fraction of mammalian H2A.Z is mono-ubiquitylated, and that on the inactive X chromosomes of female cells, the majority of this histone variant is modified by ubiquitin. Finally, ubiquitylation of H2A.Z is mediated by the RING1b E3 ligase of the human polycomb complex, further supporting a silencing role of ubiqutiylated H2A.Z (uH2A.Z). These new findings suggest that mammalian H2A.Z is associated with both euchromatin and facultative heterochromatin and that mono-ubiquitylation is a specific mark that distinguishes the H2A.Z associated with these different chromatin states.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|