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In this issue of Epigenetics

Histones are expressed as a family of sequence variants encoded by multiple genes. Histone variants contribute to nucleosomal heterogeneity and are thought to regulate a wide range of nuclear functions. The histone variant H2A.Z is found at a diversity of genomic sites that include promoters and regulatory regions of active genes, as well as constitutive and facultative heterochromatin. In this issue of Epigenetics, Hardy and Robert review the mechanisms used for the incorporation of H2A.Z into the genome. In addition to being targeted to specific genomic locations by mechanisms not fully understood, H2A.Z is also incorporated into some chromosomal regions in a random way. Randomly incorporated H2A.Z molecules are then evicted by a transcription-coupled mechanism that depletes H2A.Z from highly transcribed genes. The authors discuss the functions of H2A.Z in relation to the mechanism used for its incorporation and its interactions with other histone variants.