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Cell Rep. 2015 Nov 24;13(8):1610-22. doi: 10.1016/j.celrep.2015.10.030. Epub 2015 Nov 12.

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

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany.
4
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
5
School of Computer Science and Engineering, The Hebrew University, Jerusalem 91904, Israel; Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
6
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
7
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: craig.peterson@umassmed.edu.

Abstract

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.

PMID:
26586442
PMCID:
PMC4662874
DOI:
10.1016/j.celrep.2015.10.030
[Indexed for MEDLINE]
Free PMC Article

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