Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation

During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to whic...

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Detalles Bibliográficos
Autores: Fueyo, Raquel, Iacobucci, Simona, Pappa, Stella, Estarás, Conchi, Lois, Sergio, Vicioso Mantis, Marta, Navarro, Claudia, Cruz-Molina, Sara, Reyes, José C., Rada-Iglesias, Álvaro, Cruz, Xavier de la, Martínez-Balbás, Marian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/180513
Acceso en línea:http://hdl.handle.net/10261/180513
Access Level:acceso abierto
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spelling Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activationFueyo, RaquelIacobucci, SimonaPappa, StellaEstarás, ConchiLois, SergioVicioso Mantis, MartaNavarro, ClaudiaCruz-Molina, SaraReyes, José C.Rada-Iglesias, ÁlvaroCruz, Xavier de laMartínez-Balbás, MarianDuring neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to which extent chromatin modifiers contribute to enhancer activity is starting to be uncovered. Here, we take advantage of neural stem cells as a model to unravel the mechanisms underlying neural enhancer activation in response to the TGFβ signaling. Genome-wide experiments demonstrate that the proneural factor ASCL1 assists SMAD3 in the binding to a subset of enhancers. Once located at the enhancers, SMAD3 recruits the histone demethylase JMJD3 and the remodeling factor CHD8, creating the appropriate chromatin landscape to allow enhancer transcription and posterior gene activation. Finally, to analyze the phenotypical traits owed to cis-regulatory regions, we use CRISPR–Cas9 technology to demonstrate that the TGFβ-responsive Neurog2 enhancer is essential for proper neuronal polarization.Spanish Ministry of Education and Science [BFU2015-69248-P, BFU20012-34261 to M.M.B.]; Fundaciò La Marató de TV3 [090210 to M.M.B.]; Jérôme Lejeune Fondation; FPU fellowship and a travelling fellowship from the Company of Biologists (to R.F.). Funding for open access charge: Spanish Ministry of Education and Science [BFU2015-69248].Peer reviewedOxford University PressMinisterio de Economía y Competitividad (España)Fundació La Marató de TV3Jérôme Lejeune FoundationCompany of BiologistsConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/180513reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-69248-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-69248https://doi.org/10.1093/nar/gky093Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1805132026-05-22T06:33:51Z
dc.title.none.fl_str_mv Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
spellingShingle Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
Fueyo, Raquel
title_short Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_full Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_fullStr Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_full_unstemmed Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
title_sort Lineage specific transcription factors and epigenetic regulators mediate TGFβ-dependent enhancer activation
dc.creator.none.fl_str_mv Fueyo, Raquel
Iacobucci, Simona
Pappa, Stella
Estarás, Conchi
Lois, Sergio
Vicioso Mantis, Marta
Navarro, Claudia
Cruz-Molina, Sara
Reyes, José C.
Rada-Iglesias, Álvaro
Cruz, Xavier de la
Martínez-Balbás, Marian
author Fueyo, Raquel
author_facet Fueyo, Raquel
Iacobucci, Simona
Pappa, Stella
Estarás, Conchi
Lois, Sergio
Vicioso Mantis, Marta
Navarro, Claudia
Cruz-Molina, Sara
Reyes, José C.
Rada-Iglesias, Álvaro
Cruz, Xavier de la
Martínez-Balbás, Marian
author_role author
author2 Iacobucci, Simona
Pappa, Stella
Estarás, Conchi
Lois, Sergio
Vicioso Mantis, Marta
Navarro, Claudia
Cruz-Molina, Sara
Reyes, José C.
Rada-Iglesias, Álvaro
Cruz, Xavier de la
Martínez-Balbás, Marian
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Fundació La Marató de TV3
Jérôme Lejeune Foundation
Company of Biologists
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description During neurogenesis, dynamic developmental cues, transcription factors and histone modifying enzymes regulate the gene expression programs by modulating the activity of neural-specific enhancers. How transient developmental signals coordinate transcription factor recruitment to enhancers and to which extent chromatin modifiers contribute to enhancer activity is starting to be uncovered. Here, we take advantage of neural stem cells as a model to unravel the mechanisms underlying neural enhancer activation in response to the TGFβ signaling. Genome-wide experiments demonstrate that the proneural factor ASCL1 assists SMAD3 in the binding to a subset of enhancers. Once located at the enhancers, SMAD3 recruits the histone demethylase JMJD3 and the remodeling factor CHD8, creating the appropriate chromatin landscape to allow enhancer transcription and posterior gene activation. Finally, to analyze the phenotypical traits owed to cis-regulatory regions, we use CRISPR–Cas9 technology to demonstrate that the TGFβ-responsive Neurog2 enhancer is essential for proper neuronal polarization.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/180513
url http://hdl.handle.net/10261/180513
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-69248-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-69248
https://doi.org/10.1093/nar/gky093
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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