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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© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
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
Rege M, Subramanian V, Zhu C, Hsieh TS, Weiner A, Friedman N, Clauder-Munster S, Steinmetz LM, Rando OJ, Boyer LA, Peterson CL. (2015). Chromatin Dynamics and the RNA Exosome Function in Concert to Regulate Transcriptional Homeostasis. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.celrep.2015.10.030. Retrieved from https://escholarship.umassmed.edu/oapubs/2658
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This work is licensed under a Creative Commons Attribution 4.0 License.