Histone H2A.Z/H2A.F/Z (H2A/z) is a 128 amino acid protein encoded by the human gene H2AFZ. Eukaryotic histones are basic and water soluble nuclear proteins that form hetero-octameric nucleosome particles by wrapping 146 base pairs of DNA sequentially in a left-handed super-helical turn to form chromosomal fiber. Two molecules of each of the four core histones (H2A, H2B, H3 and H4) form the octamer, which is comprised of two H2A-H2B dimers and two H3-H4 dimers, creating two nearly symmetrical halves by tertiary structure. H2A.Z/H2A.F/Z is a variant Histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in tran-scription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of posttranslational modifications of histones, also called histone code, and nucleosome remodeling. H2A.Z/H2A.F/Z may be involved in the formation of constitutive heterochromatin and may be required for chromosome segregation during cell division.