The incorporation of histone variants into nucleosomes has important functional consequences in all aspects of eukaryotic chromatin biology. H2A.Z is a conserved histone variant found in all eukaryotes from yeast to mammals. Recent studies in yeast have shed light on the questions of where and how nucleosomes containing this variant are situated at promoters and in relation to genes, and what its specificity implies with regard to transcription. In yeast, H2A.Z appears to be primarily incorporated into the first nucleosome in the direction of transcription initiation, either of an mRNA transcript or a divergently transcribed upstream antisense non-coding RNA. This specificity of H2A.Z is due in part to the localization at promoters of SWR1, the ATP-dependent chromatin remodeler that incorporates H2A.Z into nucleosomes. Replacement of H2A.Z with canonical H2A is dependent on the function of the transcription pre-initiation complex. The recent studies summarized in this review reveal that the directionality of H2A.Z occupancy in relation to transcription thus reflects a balance of incorporation and eviction activities, which likely have varying contributions at distinct sets of genes across the genome.
Keywords: H2A.Z; Histone variant; INO80; Nucleosome; SWR1.