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The histone variant H2A.Z is a hallmark of nucleosomes flanking the promoters of protein coding genes, and is often found in nucleosomes that also carry lysine 56- acetylated histone H3 (H3-K56Ac), a mark which promotes rapid replication- independent turnover of nucleosomes. More...

The histone variant H2A.Z is a hallmark of nucleosomes flanking the promoters of protein coding genes, and is often found in nucleosomes that also carry lysine 56- acetylated histone H3 (H3-K56Ac), a mark which promotes rapid replication- independent turnover of nucleosomes. Although H2A.Z and H3-K56Ac have been generally implicated in transcriptional activation, their exact contributions have remained elusive. Here we find that H3-K56Ac promotes RNA polymerase II occupancy at a large number of protein coding and noncoding loci, yet neither H3- K56Ac nor H2A.Z has a significant impact on steady state mRNA levels in yeast. Instead, broad effects of H3-K56Ac or H2A.Z on levels of both coding and noncoding RNAs (ncRNAs) are only revealed in the absence of the nuclear RNA exosome. H2A.Z is also necessary for expression of divergent, promoter-proximal ncRNAs in mouse embryonic stem cells, suggesting a conserved role for H2A.Z across eukaryotes. Finally, we show that H2A.Z functions with H3-K56Ac in chromosome folding, facilitating formation of chromosome interaction domains (CIDs). Our study suggests that H2A.Z and H3-K56Ac work in concert with the RNA exosome to control mRNA and ncRNA expression, perhaps in part by regulating higher order chromatin structures. Overall design: Total RNA isolated from 27 samples with replicates of each strain ranging from 2 to 5. 12 samples from the Proudfoot lab [deposited in ArrayExpress, accession number E-TABM-936] were downloaded as .CEL files and analyzed alongside samples generated in this study. The identical processing for used for both sets of samples. For details refer to supplementary methods in the paper. Less...