The histone variant H2A.Z is a hallmark of nucleosomes flanking promoters of protein-coding genes and is often found in nucleosomes that carry lysine 56-acetylated histone H3 (H3-K56Ac), a mark that promotes replication-independent nucleosome turnover. Here, we find that H3-K56Ac promotes RNA polymerase II occupancy at many 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 RNA levels are revealed only in the absence of the nuclear RNA exosome. H2A.Z is also necessary for the expression of divergent, promoter-proximal noncoding RNAs (ncRNAs) in mouse embryonic stem cells. Finally, we show that H2A.Z functions with H3-K56Ac to facilitate 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. The histone modification H3-K56Ac and variant H2A.Z are known to enhance chromatin dynamics. Here, Rege et al. find that these features have global impacts on coding and noncoding RNA expression only after RNA exosome inactivation. This may be due, in part, to their roles in the formation of chromosome interaction domains.
Bibliographical noteFunding Information:
We thank Dirk Schiebler (IMP, Basel) for suggesting the model shown in Figure 6 , Jon-Matthew Belton for sharing the 3C protocol, Alper Kucukural (UMass, Worcester), Varun Aggarwala (UPenn), and Andy Rampersaud (Boston University) for discussions about ChIP-seq data analysis. This work was supported by grants from the National Institutes of Health to C.L.P. (GM049650) and O.J.R. (R01GM079205) and by grants from the Deutsche Forschungsgemeinschaft and a European Research Council Advanced Investigator Grant to L.M.S.
© 2015 The Authors.