title: Chromatin Dynamics and the RNA Exosome Function in Concert to Regulate Transcriptional Homeostasis.
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.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Mayuri
authors.initials: M
authors.lastname: Rege
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Subramanian
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Tsung-Han S
authors.initials: TH
authors.lastname: Hsieh
authors.affiliation: School of Computer Science and Engineering, The Hebrew University, Jerusalem 91904, Israel; Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Weiner
authors.affiliation: School of Computer Science and Engineering, The Hebrew University, Jerusalem 91904, Israel; Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Clauder-Münster
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Boyer
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: craig.peterson@umassmed.edu.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Peterson
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics*; D006657:Histones / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D051379:Mice; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012333:RNA, Messenger; D022661:RNA, Untranslated; D063326:Exosome Multienzyme Ribonuclease Complex