title: Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF.
abstract: Approximately 75% of the human genome is transcribed, the majority of which does not encode protein. However, many noncoding RNAs (ncRNAs) are rapidly degraded after transcription, and relatively few have established functions, questioning the significance of this observation. Here we show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of ncRNAs from ∼57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells (ESCs). We show that esBAF functions to both keep NDRs nucleosome-free and promote elevated nucleosome occupancy adjacent to NDRs. Reduction of adjacent nucleosome occupancy upon esBAF depletion is strongly correlated with ncRNA expression, suggesting that flanking nucleosomes form a barrier to pervasive transcription. Upon forcing nucleosome occupancy near two NDRs using a nucleosome-positioning sequence, we found that esBAF is no longer required to silence transcription. Therefore, esBAF's function to enforce nucleosome occupancy adjacent to NDRs, and not its function to maintain NDRs in a nucleosome-free state, is necessary for silencing transcription over ncDNA. Finally, we show that the ability of a strongly positioned nucleosome to repress ncRNA depends on its translational positioning. These data reveal a novel role for esBAF in suppressing pervasive transcription from open chromatin regions in ESCs.
authors.affiliation: Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Hainer
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Weifeng
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Carone
authors.affiliation: Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Landry
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
authors.affiliation: Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; thomas.fazzio@umassmed.edu.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Fazzio
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D022661:RNA, Untranslated; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: chromatin remodeling; esBAF; ncRNA; nucleosome occupancy; transcription