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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2019
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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. |
format | Online Article Text |
id | pubmed-6859502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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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