Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences
Biochemistry | Molecular Biology | Molecular Genetics
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.
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Citation: Cell Rep. 2015 Nov 24;13(8):1610-22. doi: 10.1016/j.celrep.2015.10.030. Epub 2015 Nov 12. Link to article on publisher's site
DOI of Published Version
Rege, Mayuri; Subramanian, Vidya; Zhu, Chenchen; Hsieh, Tsung-Han S.; Weiner, Assaf; Friedman, Nir; Clauder-Munster, Sandra; Steinmetz, Lars M.; Rando, Oliver J.; Boyer, Laurie A.; and Peterson, Craig L., "Chromatin Dynamics and the RNA Exosome Function in Concert to Regulate Transcriptional Homeostasis" (2015). Open Access Articles. 2658.
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