EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21

The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor prolifer...

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Autores: Akizu, Naiara, García, María Alejandra, Estarás, Conchi, Fueyo, Raquel, Badosa, Carmen, Cruz, Xavier de la, Martínez-Balbás, Marian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/133759
Acceso en línea:http://hdl.handle.net/10261/133759
Access Level:acceso abierto
Palabra clave:Neuroblast proliferation
Neural development
EZH2
Gene silencing
Histone methylation
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spelling EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21Akizu, NaiaraGarcía, María AlejandraEstarás, ConchiFueyo, RaquelBadosa, CarmenCruz, Xavier de laMartínez-Balbás, MarianNeuroblast proliferationNeural developmentEZH2Gene silencingHistone methylationThe function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor proliferation. We demonstrate that knocking down the EZH2 in chick embryo neural tubes unexpectedly disrupts the neuroepithelium (NE) structure, correlating with alteration of the Rho pathway, and reduces neural progenitor proliferation. Moreover, we use transcriptional profiling and functional assays to show that EZH2-mediated repression of p21contributes to both processes. Accordingly, overexpression of cytoplasmic p21induces NE structural alterations and p21suppression rescues proliferation defects and partially compensates for the structural alterations and the Rho activity. Overall, our findings describe a new role of EZH2 in controlling the NE integrity in the neural tube to allow proper progenitor proliferation.This study was supported by grants CSD2006-00049, BFU2009-11527, BFU-2012-34261 to M.A.M.-B. and BFU2009-11527 and BIO2006-15557 to X.C. from the Spanish Ministry of Education and Science, 090210 from Fundaciò La Marató de TV3 and Fondation Jérôme Lejeune to M.A.M.-B. and 200420E578 from the CSIC to X.C. N.A., C.E. and M.A.G. received an I3P fellowship (I3P-BPD2005) and FPU fellowship, respectivelyPeer ReviewedRoyal Society (Great Britain)Jérôme Lejeune FoundationFundació La Marató de TV3Ministerio de Educación y Ciencia (España)Consejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2016201620162016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/133759reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1098/rsob.150227Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1337592026-05-22T06:33:51Z
dc.title.none.fl_str_mv EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
title EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
spellingShingle EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
Akizu, Naiara
Neuroblast proliferation
Neural development
EZH2
Gene silencing
Histone methylation
title_short EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
title_full EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
title_fullStr EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
title_full_unstemmed EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
title_sort EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
dc.creator.none.fl_str_mv Akizu, Naiara
García, María Alejandra
Estarás, Conchi
Fueyo, Raquel
Badosa, Carmen
Cruz, Xavier de la
Martínez-Balbás, Marian
author Akizu, Naiara
author_facet Akizu, Naiara
García, María Alejandra
Estarás, Conchi
Fueyo, Raquel
Badosa, Carmen
Cruz, Xavier de la
Martínez-Balbás, Marian
author_role author
author2 García, María Alejandra
Estarás, Conchi
Fueyo, Raquel
Badosa, Carmen
Cruz, Xavier de la
Martínez-Balbás, Marian
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Jérôme Lejeune Foundation
Fundació La Marató de TV3
Ministerio de Educación y Ciencia (España)
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Neuroblast proliferation
Neural development
EZH2
Gene silencing
Histone methylation
topic Neuroblast proliferation
Neural development
EZH2
Gene silencing
Histone methylation
description The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor proliferation. We demonstrate that knocking down the EZH2 in chick embryo neural tubes unexpectedly disrupts the neuroepithelium (NE) structure, correlating with alteration of the Rho pathway, and reduces neural progenitor proliferation. Moreover, we use transcriptional profiling and functional assays to show that EZH2-mediated repression of p21contributes to both processes. Accordingly, overexpression of cytoplasmic p21induces NE structural alterations and p21suppression rescues proliferation defects and partially compensates for the structural alterations and the Rho activity. Overall, our findings describe a new role of EZH2 in controlling the NE integrity in the neural tube to allow proper progenitor proliferation.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
2016
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/10261/133759
url http://hdl.handle.net/10261/133759
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1098/rsob.150227
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Royal Society (Great Britain)
publisher.none.fl_str_mv Royal Society (Great Britain)
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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score 15,811543

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