title: Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
abstract: ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Maud
authors.initials: M
authors.lastname: de Dieuleveult
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Kuangyu
authors.initials: K
authors.lastname: Yen
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hmitou
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Depaux
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.|INSERM, U823; Université Grenoble Alpes; Institut Albert Bonniot Grenoble, 38700 Grenoble, France.
authors.forename: Fayçal
authors.initials: F
authors.lastname: Boussouar
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Daria
authors.initials: D
authors.lastname: Bou Dargham
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jounier
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Humbertclaude
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, 91057 Evry, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ribierre
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, 91057 Evry, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Baulard
authors.affiliation: Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Nina P
authors.initials: NP
authors.lastname: Farrell
authors.affiliation: Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Bongsoo
authors.initials: B
authors.lastname: Park
authors.affiliation: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), INSERM, U964, CNRS, UMR7104, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Keime
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrière
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Soizick
authors.initials: S
authors.lastname: Berlivet
authors.affiliation: Centre Nacional D'Anàlisi Genòmica, 08028 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.affiliation: Centre Nacional D'Anàlisi Genòmica, 08028 Barcelona, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Werner
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, 91057 Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, 91057 Evry, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Olaso
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Aude
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, 91057 Evry, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chantalat
authors.affiliation: Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: B Franklin
authors.initials: BF
authors.lastname: Pugh
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Gérard
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D051379:Mice; D008836:Micrococcal Nuclease / Q000378:metabolism; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D013379:Substrate Specificity; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D004265:DNA Helicases; D004268:DNA-Binding Proteins; D006657:Histones; D008836:Micrococcal Nuclease; D009687:Nuclear Proteins; D009707:Nucleosomes; D012319:RNA Polymerase II; D015534:Trans-Activators; D014157:Transcription Factors; C489844:Chd1 protein, mouse; C514205:Chd2 protein, mouse; C499332:Ep400 protein, mouse; C515814:duplin protein, mouse; C513194:Smarca4 protein, mouse; C509277:Mi-2beta protein, mouse; C550983:Chd6 protein, mouse; C511083:Chd9 protein, mouse
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