Discriminating nucleosomes containing histone H2A.Z or H2A based on genetic and epigenetic information

Nucleosomes are nucleoproteic complexes, formed of eight histone molecules and DNA, and they are responsible for the compaction of the eukaryotic genome. Their presence on DNA influences many cellular processes, such as transcription, DNA replication, and DNA repair. The evolutionarily conserved histone variant H2A.Z alters nucleosome stability and is highly enriched at gene promoters. Its localization to specific genomic loci in human cells is presumed to depend either on the underlying DNA sequence or on a certain epigenetic modification pattern.

We analyzed the differences in histone post-translational modifications and DNA sequences near nucleosomes that do or do not contain H2A.Z. We show that both the epigenetic context and underlying sequences can be used to classify nucleosomal regions, with highly significant accuracy, as likely to either contain H2A.Z or canonical histone H2A. Furthermore, our models accurately recapitulate the observed nucleosome occupancy near the transcriptional start sites of human promoters.

We conclude that both genetic and epigenetic features are likely to participate in targeting H2A.Z to distinct chromatin loci.