title: Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis.
abstract: 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.
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Alexandre A S F
authors.initials: AASF
authors.lastname: Raposo
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Francisca F
authors.initials: FF
authors.lastname: Vasconcelos
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Drechsel
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR-S 1127, Institut du Cerveau et de la Moelle Épinière, ICM, 75013 Paris, France.
authors.forename: Corentine
authors.initials: C
authors.lastname: Marie
authors.affiliation: Centre for the Cellular Basis of Behavior, Institute of Psychiatry, King's College London, London SE5 9NU, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Johnston
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK; Wellcome Trust Sanger Institute, Welcome Trust Genome Campus, Cambridge CB10 1SA, UK.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dolle
authors.affiliation: University of Reading, School of Pharmacy, Hopkins Life Sciences Building, Reading RG6 6AP, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Bithell
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gillotin
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Debbie L C
authors.initials: DLC
authors.lastname: van den Berg
authors.affiliation: Centre for Organismal Studies (COS), Ruprecht-Karls-University, 69120 Heidelberg, Germany.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ettwiller
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK; Wellcome Trust Sanger Institute, Welcome Trust Genome Campus, Cambridge CB10 1SA, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.affiliation: Institute of Genome Sciences & Policy, Duke University, Durham, NC 27708, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR-S 1127, Institut du Cerveau et de la Moelle Épinière, ICM, 75013 Paris, France.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Parras
authors.affiliation: Institute of Physiological Chemistry, University Medical Center Johannes Gutenberg University Mainz, 55128 Mainz, Germany; Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
authors.forename: Noel J
authors.initials: NJ
authors.lastname: Buckley
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal. Electronic address: dscastro@igc.gulbenkian.pt.
authors.forename: Diogo S
authors.initials: DS
authors.lastname: Castro