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Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis

Title: Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis
Authors: Raposo, Alexandre a.S.F.; Vasconcelos, Francisca f.; Drechsel, Daniela; Marie, Corentine; Johnston, Caroline; Dolle, Dirk; Bithell, Angela; Gillotin, Sébastien; Van den berg, Debbie l.C.; Ettwiller, Laurence; Flicek, Paul; Crawford, Gregory e.; Parras, Carlos m.; Berninger, Benedikt; Buckley, Noel j.; Guillemot, François; Castro, Diogo s.
Contributors: Instituto Gulbenkian de Ciência Oeiras (IGC); Fundação Calouste Gulbenkian = Fondation Calouste Gulbenkian = Calouste Gulbenkian Foundation Lisbonne; MRC National Institute for Medical Research; Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM); Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Centre for the Cellular Basis of Behavior; European Molecular Biology Laboratory; European Bioinformatics Institute; The Wellcome Trust Sanger Institute Cambridge; University of Reading (UOR); Centre for Organismal Studies EMBL (COS); Universität Heidelberg Heidelberg = Heidelberg University; Duke University Durham; Surgical Department of the LMU Munich; Institute of Physiological Chemistry; Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU); Department of Psychiatry Oxford (POWIC); University of Oxford-Warneford Hospital Oxford (WH)
Source: ISSN: 2211-1247.
Publisher Information: CCSD; Elsevier Inc
Publication Year: 2015
Subject Terms: [SDV.BBM]Life Sciences [q-bio]/Biochemistry; Molecular Biology
Description: International audience ; The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1016/j.celrep.2015.02.025
Availability: https://hal.sorbonne-universite.fr/hal-01213854; https://hal.sorbonne-universite.fr/hal-01213854v1/document; https://hal.sorbonne-universite.fr/hal-01213854v1/file/1-s2.0-S2211124715001710-main.pdf; https://doi.org/10.1016/j.celrep.2015.02.025
Rights: http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.C6892FA4
Database: BASE