Publication Date:
2016-01-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Dieuleveult, Maud -- Yen, Kuangyu -- Hmitou, Isabelle -- Depaux, Arnaud -- Boussouar, Faycal -- Dargham, Daria Bou -- Jounier, Sylvie -- Humbertclaude, Helene -- Ribierre, Florence -- Baulard, Celine -- Farrell, Nina P -- Park, Bongsoo -- Keime, Celine -- Carriere, Lucie -- Berlivet, Soizick -- Gut, Marta -- Gut, Ivo -- Werner, Michel -- Deleuze, Jean-Francois -- Olaso, Robert -- Aude, Jean-Christophe -- Chantalat, Sophie -- Pugh, B Franklin -- Gerard, Matthieu -- HG004160/HG/NHGRI NIH HHS/ -- R01 HG004160/HG/NHGRI NIH HHS/ -- England -- Nature. 2016 Feb 4;530(7588):113-6. doi: 10.1038/nature16505. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Universite Paris-Sud, Universite Paris-Saclay, 91198 Gif-sur-Yvette, France. ; 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. ; INSERM, U823; Universite Grenoble Alpes; Institut Albert Bonniot Grenoble, 38700 Grenoble, France. ; Centre National de Genotypage, Institut de Genomique, CEA, 91057 Evry, France. ; IGBMC (Institut de Genetique et de Biologie Moleculaire et Cellulaire), INSERM, U964, CNRS, UMR7104, Universite de Strasbourg, 67404 Illkirch, France. ; Centre Nacional D'Analisi Genomica, 08028 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814966" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Chromatin Assembly and Disassembly
;
DNA Helicases/metabolism
;
DNA-Binding Proteins/*metabolism
;
*Gene Expression Regulation
;
Genome/*genetics
;
Histones/metabolism
;
Mice
;
Micrococcal Nuclease/metabolism
;
Mouse Embryonic Stem Cells/cytology/*metabolism
;
Nuclear Proteins/metabolism
;
Nucleosomes/*genetics/*metabolism
;
Promoter Regions, Genetic/genetics
;
RNA Polymerase II/metabolism
;
Substrate Specificity
;
Trans-Activators/metabolism
;
Transcription Factors/metabolism
;
Transcription Initiation Site
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
