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Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways.

Authors
  • Bonnefont, Jerome1
  • Tiberi, Luca2
  • van den Ameele, Jelle2
  • Potier, Delphine3
  • Gaber, Zachary B4
  • Lin, Xionghui2
  • Bilheu, Angéline2
  • Herpoel, Adèle2
  • Velez Bravo, Fausto D1
  • Guillemot, François4
  • Aerts, Stein3
  • Vanderhaeghen, Pierre5
  • 1 Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium. , (Belgium)
  • 2 Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium. , (Belgium)
  • 3 VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium. , (Belgium)
  • 4 The Francis Crick Institute, London NW1 1AT, UK.
  • 5 Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Welbio, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium. Electronic address: [email protected] , (Belgium)
Type
Published Article
Journal
Neuron
Publication Date
Sep 25, 2019
Volume
103
Issue
6
Identifiers
DOI: 10.1016/j.neuron.2019.06.027
PMID: 31353074
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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