Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation

Pluripotency is regulated by a network of transcription factors that maintain early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. H...

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Detalhes bibliográficos
Autores: Barral, Antonio, Rollan, isabel, Sánchez-Iranzo, Héctor, Jawaid, Wajid, Badía-Careaga, Claudio, Menchero, Sergio, Gómez, Manuel J., Torroja, Carlos, Sánchez-Cabo, Fátima, Göttgens, Berthold, Manzanares, Miguel, Sainz de Aja, Julio
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/215090
Acesso em linha:http://hdl.handle.net/10261/215090
Access Level:acceso abierto
Palavra-chave:Nanog
Pou3f1
Pluripotency
Epiblast
Regulatory
Genomics
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spelling Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulationBarral, AntonioRollan, isabelSánchez-Iranzo, HéctorJawaid, WajidBadía-Careaga, ClaudioMenchero, SergioGómez, Manuel J.Torroja, CarlosSánchez-Cabo, FátimaGöttgens, BertholdManzanares, MiguelSainz de Aja, JulioNanogPou3f1PluripotencyEpiblastRegulatoryGenomicsPluripotency is regulated by a network of transcription factors that maintain early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development is its expression restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses genes involved in anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog. Use of Nanog null ES cells further demonstrated a role for Nanog in repressing a subset of anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting neural regulatory networks by repressing Pou3f1 at the onset of gastrulation.Spanish government [grant BFU2017-84914-P to M.M.]. The Gottgens laboratory is supported by core funding from the Wellcome Trust and Medical Research Council to the Wellcome and Medical Research Council Cambridge Stem Cell Institute. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence [SEV-2015-0505]Company of BiologistsMedical Research Council (UK)MRC Cambridge Stem Cell InstituteInstituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y Universidades (España)Centro Nacional de Investigaciones Cardiovasculares (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/215090reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1242/bio.046367Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2150902026-05-22T06:33:51Z
dc.title.none.fl_str_mv Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
title Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
spellingShingle Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
Barral, Antonio
Nanog
Pou3f1
Pluripotency
Epiblast
Regulatory
Genomics
title_short Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
title_full Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
title_fullStr Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
title_full_unstemmed Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
title_sort Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
dc.creator.none.fl_str_mv Barral, Antonio
Rollan, isabel
Sánchez-Iranzo, Héctor
Jawaid, Wajid
Badía-Careaga, Claudio
Menchero, Sergio
Gómez, Manuel J.
Torroja, Carlos
Sánchez-Cabo, Fátima
Göttgens, Berthold
Manzanares, Miguel
Sainz de Aja, Julio
author Barral, Antonio
author_facet Barral, Antonio
Rollan, isabel
Sánchez-Iranzo, Héctor
Jawaid, Wajid
Badía-Careaga, Claudio
Menchero, Sergio
Gómez, Manuel J.
Torroja, Carlos
Sánchez-Cabo, Fátima
Göttgens, Berthold
Manzanares, Miguel
Sainz de Aja, Julio
author_role author
author2 Rollan, isabel
Sánchez-Iranzo, Héctor
Jawaid, Wajid
Badía-Careaga, Claudio
Menchero, Sergio
Gómez, Manuel J.
Torroja, Carlos
Sánchez-Cabo, Fátima
Göttgens, Berthold
Manzanares, Miguel
Sainz de Aja, Julio
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medical Research Council (UK)
MRC Cambridge Stem Cell Institute
Instituto de Salud Carlos III
Ministerio de Ciencia, Innovación y Universidades (España)
Centro Nacional de Investigaciones Cardiovasculares (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Nanog
Pou3f1
Pluripotency
Epiblast
Regulatory
Genomics
topic Nanog
Pou3f1
Pluripotency
Epiblast
Regulatory
Genomics
description Pluripotency is regulated by a network of transcription factors that maintain early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development is its expression restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses genes involved in anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog. Use of Nanog null ES cells further demonstrated a role for Nanog in repressing a subset of anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting neural regulatory networks by repressing Pou3f1 at the onset of gastrulation.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
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/10261/215090
url http://hdl.handle.net/10261/215090
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1242/bio.046367
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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 15,81155

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