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

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 demonst...

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Autores principales: Bonnefont, Jerome, Tiberi, Luca, van den Ameele, Jelle, Potier, Delphine, Gaber, Zachary B., Lin, Xionghui, Bilheu, Angéline, Herpoel, Adèle, Velez Bravo, Fausto D., Guillemot, François, Aerts, Stein, Vanderhaeghen, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859502/
https://www.ncbi.nlm.nih.gov/pubmed/31353074
http://dx.doi.org/10.1016/j.neuron.2019.06.027
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author Bonnefont, Jerome
Tiberi, Luca
van den Ameele, Jelle
Potier, Delphine
Gaber, Zachary B.
Lin, Xionghui
Bilheu, Angéline
Herpoel, Adèle
Velez Bravo, Fausto D.
Guillemot, François
Aerts, Stein
Vanderhaeghen, Pierre
author_facet Bonnefont, Jerome
Tiberi, Luca
van den Ameele, Jelle
Potier, Delphine
Gaber, Zachary B.
Lin, Xionghui
Bilheu, Angéline
Herpoel, Adèle
Velez Bravo, Fausto D.
Guillemot, François
Aerts, Stein
Vanderhaeghen, Pierre
author_sort Bonnefont, Jerome
collection PubMed
description 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.
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spelling pubmed-68595022019-11-22 Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways Bonnefont, Jerome Tiberi, Luca van den Ameele, Jelle Potier, Delphine Gaber, Zachary B. Lin, Xionghui Bilheu, Angéline Herpoel, Adèle Velez Bravo, Fausto D. Guillemot, François Aerts, Stein Vanderhaeghen, Pierre Neuron Article 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. Cell Press 2019-09-25 /pmc/articles/PMC6859502/ /pubmed/31353074 http://dx.doi.org/10.1016/j.neuron.2019.06.027 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Bonnefont, Jerome
Tiberi, Luca
van den Ameele, Jelle
Potier, Delphine
Gaber, Zachary B.
Lin, Xionghui
Bilheu, Angéline
Herpoel, Adèle
Velez Bravo, Fausto D.
Guillemot, François
Aerts, Stein
Vanderhaeghen, Pierre
Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
title Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
title_full Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
title_fullStr Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
title_full_unstemmed Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
title_short Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
title_sort cortical neurogenesis requires bcl6-mediated transcriptional repression of multiple self-renewal-promoting extrinsic pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859502/
https://www.ncbi.nlm.nih.gov/pubmed/31353074
http://dx.doi.org/10.1016/j.neuron.2019.06.027
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