Abstract

Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites, but the mechanistic basis for enrichment is unknown. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotypic). To elucidate H2A.Z function, we generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2A.Z nucleosomes map throughout most of the genome, homotypic nucleosomes are enriched and heterotypic nucleosomes are depleted downstream of active promoters and intron/exon junctions. The distribution of homotypic H2A.Z nucleosomes resembles that of classical active chromatin and shows evidence of disruption during transcriptional elongation. Both homotypic H2A.Z nucleosomes and classical active chromatin are depleted downstream of paused polymerases. Our results suggest that H2A.Z enrichment patterns result from intrinsic structural differences between heterotypic and homotypic H2A.Z nucleosomes following disruption during transcriptional elongation.

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