H2AZ

Histone H2A.Z is a variant of histone H2A that is incorporated into nucleosomes and influences chromatin structure and gene regulation in eukaryotic cells. In vertebrates, two paralogs are expressed, commonly referred to as H2A.Z.1 and H2A.Z.2, encoded by distinct genes. H2A.Z differs from canonical H2A in its N-terminal region and its docking domain, which modulate nucleosome stability and interactions with chromatin modifiers. The variant is deposited into chromatin by ATP-dependent remodeling complexes; in yeast SWR1 and in mammals by SRCAP and related complexes such as p400/Tip60, which exchange H2A with H2A.Z at targeted loci.

H2A.Z is enriched at promoters, especially the first downstream nucleosome (+1), and at regulatory elements such as enhancers. Its presence generally correlates with active or poised transcription and it is thought to help define promoter architecture, regulate nucleosome occupancy, and facilitate recruitment of transcription machinery. Post-translational modifications, including acetylation and ubiquitination of H2A.Z, modulate its effect on transcription and chromatin dynamics. Acetylation is commonly associated with gene activation, while other modifications can contribute to repression or complex regulatory outcomes.

Biological roles of H2A.Z include participation in development and differentiation, genome stability, and DNA damage response. Proper deposition and turnover of H2A.Z are important for normal gene expression programs; perturbations can lead to altered expression patterns and cellular phenotypes. In humans, the two H2A.Z paralogs can have partly distinct functions, and dysregulation of H2A.Z variants has been linked to cancer in some contexts.