Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/418 |
Resumo: | The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program. |
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Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during NeurogenesisAscl1NeurogenesisDNAThe proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.FCT doctoral fellowship, FCT investigator program, Marie Curie CIG: (303644), Welcome Trust grants: (WT095908, WT098051).Cell PressARCARaposo, Alexandre A.S.F.Vasconcelos, Francisca F.Drechsel, DanielaMarie, CorentineJohnston, CarolineDolle, DirkBithell, AngelaGillotin, Sébastienvan den Berg, Debbie L.C.Ettwiller, LaurenceFlicek, PaulCrawford, Gregory E.Parras, Carlos M.Berninger, BenediktBuckley, Noel J.Guillemot, FrançoisCastro, Diogo S.2015-10-21T10:17:49Z2015-03-042015-03-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/418eng10.1016/j.celrep.2015.02.025info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:34:48Zoai:arca.igc.gulbenkian.pt:10400.7/418Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:42.782220Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
title |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
spellingShingle |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis Raposo, Alexandre A.S.F. Ascl1 Neurogenesis DNA |
title_short |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
title_full |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
title_fullStr |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
title_full_unstemmed |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
title_sort |
Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis |
author |
Raposo, Alexandre A.S.F. |
author_facet |
Raposo, Alexandre A.S.F. Vasconcelos, Francisca F. Drechsel, Daniela Marie, Corentine Johnston, Caroline Dolle, Dirk Bithell, Angela Gillotin, Sébastien van den Berg, Debbie L.C. Ettwiller, Laurence Flicek, Paul Crawford, Gregory E. Parras, Carlos M. Berninger, Benedikt Buckley, Noel J. Guillemot, François Castro, Diogo S. |
author_role |
author |
author2 |
Vasconcelos, Francisca F. Drechsel, Daniela Marie, Corentine Johnston, Caroline Dolle, Dirk Bithell, Angela Gillotin, Sébastien van den Berg, Debbie L.C. Ettwiller, Laurence Flicek, Paul Crawford, Gregory E. Parras, Carlos M. Berninger, Benedikt Buckley, Noel J. Guillemot, François Castro, Diogo S. |
author2_role |
author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Raposo, Alexandre A.S.F. Vasconcelos, Francisca F. Drechsel, Daniela Marie, Corentine Johnston, Caroline Dolle, Dirk Bithell, Angela Gillotin, Sébastien van den Berg, Debbie L.C. Ettwiller, Laurence Flicek, Paul Crawford, Gregory E. Parras, Carlos M. Berninger, Benedikt Buckley, Noel J. Guillemot, François Castro, Diogo S. |
dc.subject.por.fl_str_mv |
Ascl1 Neurogenesis DNA |
topic |
Ascl1 Neurogenesis DNA |
description |
The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10-21T10:17:49Z 2015-03-04 2015-03-04T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/418 |
url |
http://hdl.handle.net/10400.7/418 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1016/j.celrep.2015.02.025 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Cell Press |
publisher.none.fl_str_mv |
Cell Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
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1799130572885327872 |