Chromatin Dynamics and the RNA Exosome Function in Concert to Regulate Transcriptional Homeostasis

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 polyme...

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Bibliographic Details
Main Authors: Rege, Mayuri, Subramanian, Vidya, Zhu, Chenchen, Hsieh, Tsung-Han S., Weiner, Assaf, Friedman, Nir, Steinmetz, Lars M., Rando, Oliver J., Peterson, Craig L., Clauder-Munster, Sandra, Boyer, Laurie Ann
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Elsevier 2016
Online Access:http://hdl.handle.net/1721.1/101704
https://orcid.org/0000-0003-3491-4962
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Summary: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.