Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters
Autor(a) principal: | |
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Data de Publicação: | 2012 |
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/10400.18/917 |
Resumo: | Gene expression depends on binding of transcriptional regulators to gene promoters, a process controlled by signalling pathways. The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1. Interestingly, the DNA motifs recognized by BCL-6 and signal transducers and activators of transcription 5 (STAT5) are similar. Because STAT5 stimulation in epithelial cells can also be triggered by Rac1 signalling, we asked whether both factors have opposing roles in transcriptional regulation and whether Rac1 signalling may coordinate a transcription factor switch. We used chromatin immunoprecipitation to show that active Rac1 promotes release of the repressor BCL-6 while increasing binding of STAT5A to a BCL-6-regulated reporter gene. We further show in colorectal cell lines that the endogenous activation status of the Rac1/PAK1 pathway correlated with the phosphorylation status of BCL-6 and STAT5A. Three cellular genes (cyclin D2, p15INK4B, small ubiquitin-like modifier 1) were identified to be inversely regulated by BCL-6 and STAT5A and responded to Rac1 signalling with increased expression and corresponding changes in promoter occupancy. Together, our data show that Rac1 signalling controls a group of target genes that are repressed by BCL-6 and activated by STAT5A, providing novel insights into the modulation of gene transcription by GTPase signalling. |
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Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promotersVias de Transdução de Sinal e Patologias AssociadasRac1Gene ExpressionSTAT5BCL-6Chromatin ImmunoprecipitationGene expression depends on binding of transcriptional regulators to gene promoters, a process controlled by signalling pathways. The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1. Interestingly, the DNA motifs recognized by BCL-6 and signal transducers and activators of transcription 5 (STAT5) are similar. Because STAT5 stimulation in epithelial cells can also be triggered by Rac1 signalling, we asked whether both factors have opposing roles in transcriptional regulation and whether Rac1 signalling may coordinate a transcription factor switch. We used chromatin immunoprecipitation to show that active Rac1 promotes release of the repressor BCL-6 while increasing binding of STAT5A to a BCL-6-regulated reporter gene. We further show in colorectal cell lines that the endogenous activation status of the Rac1/PAK1 pathway correlated with the phosphorylation status of BCL-6 and STAT5A. Three cellular genes (cyclin D2, p15INK4B, small ubiquitin-like modifier 1) were identified to be inversely regulated by BCL-6 and STAT5A and responded to Rac1 signalling with increased expression and corresponding changes in promoter occupancy. Together, our data show that Rac1 signalling controls a group of target genes that are repressed by BCL-6 and activated by STAT5A, providing novel insights into the modulation of gene transcription by GTPase signalling.Fundação para a Ciência e Tecnologia, Portugal [PPCDT/SAU-OBS/57660/2004] (to P.J.), [PTDC/SAU-GMG/119586/2010] (to P.M.), [PEst-OE/BIA/UI4046/2011] (to the BioFig research unit)Oxford University PressRepositório Científico do Instituto Nacional de SaúdeBarros, PatríciaLam, Eric W-FJordan, PeterMatos, Paulo2012-07-10T16:15:17Z2012-072012-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/917engNucleic Acids Res. 2012 Sep 1;40(16):7776-87. Epub 2012 Jun 20.0305-1048doi:10.1093/nar/gks571info: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:RCAAP2023-07-20T15:38:27Zoai:repositorio.insa.pt:10400.18/917Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:36:06.270337Repositório 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 |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
title |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
spellingShingle |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters Barros, Patrícia Vias de Transdução de Sinal e Patologias Associadas Rac1 Gene Expression STAT5 BCL-6 Chromatin Immunoprecipitation |
title_short |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
title_full |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
title_fullStr |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
title_full_unstemmed |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
title_sort |
Rac1 signalling modulates a STAT5/BCL-6 transcriptional switch on cell cycle-associated target gene promoters |
author |
Barros, Patrícia |
author_facet |
Barros, Patrícia Lam, Eric W-F Jordan, Peter Matos, Paulo |
author_role |
author |
author2 |
Lam, Eric W-F Jordan, Peter Matos, Paulo |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Barros, Patrícia Lam, Eric W-F Jordan, Peter Matos, Paulo |
dc.subject.por.fl_str_mv |
Vias de Transdução de Sinal e Patologias Associadas Rac1 Gene Expression STAT5 BCL-6 Chromatin Immunoprecipitation |
topic |
Vias de Transdução de Sinal e Patologias Associadas Rac1 Gene Expression STAT5 BCL-6 Chromatin Immunoprecipitation |
description |
Gene expression depends on binding of transcriptional regulators to gene promoters, a process controlled by signalling pathways. The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1. Interestingly, the DNA motifs recognized by BCL-6 and signal transducers and activators of transcription 5 (STAT5) are similar. Because STAT5 stimulation in epithelial cells can also be triggered by Rac1 signalling, we asked whether both factors have opposing roles in transcriptional regulation and whether Rac1 signalling may coordinate a transcription factor switch. We used chromatin immunoprecipitation to show that active Rac1 promotes release of the repressor BCL-6 while increasing binding of STAT5A to a BCL-6-regulated reporter gene. We further show in colorectal cell lines that the endogenous activation status of the Rac1/PAK1 pathway correlated with the phosphorylation status of BCL-6 and STAT5A. Three cellular genes (cyclin D2, p15INK4B, small ubiquitin-like modifier 1) were identified to be inversely regulated by BCL-6 and STAT5A and responded to Rac1 signalling with increased expression and corresponding changes in promoter occupancy. Together, our data show that Rac1 signalling controls a group of target genes that are repressed by BCL-6 and activated by STAT5A, providing novel insights into the modulation of gene transcription by GTPase signalling. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-07-10T16:15:17Z 2012-07 2012-07-01T00:00:00Z |
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/10400.18/917 |
url |
http://hdl.handle.net/10400.18/917 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nucleic Acids Res. 2012 Sep 1;40(16):7776-87. Epub 2012 Jun 20. 0305-1048 doi:10.1093/nar/gks571 |
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 |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University 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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1799132090340474880 |