Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation

Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins...

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Autores: Bertucci, Paola Y., Nacht, A. Silvina, Alló, Mariano, Rocha-Viegas, Luciana, Ballaré, Cecilia Julia, Soronellas, Daniel, Castellano, Giancarlo, Zaurín Quer, Roser, Kornblihtt, Alberto R., Beato, Miguel, Vicent, Guillermo Pablo, Pecci, Adali
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/58299
Acceso en línea:http://hdl.handle.net/10230/58299
http://dx.doi.org/10.1093/nar/gkt327
Access Level:acceso abierto
Palabra clave:Progesterona -- Receptors
Esteroides
Hormones esteroides
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spelling Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongationBertucci, Paola Y.Nacht, A. SilvinaAlló, MarianoRocha-Viegas, LucianaBallaré, Cecilia JuliaSoronellas, DanielCastellano, GiancarloZaurín Quer, RoserKornblihtt, Alberto R.Beato, MiguelVicent, Guillermo PabloPecci, AdaliProgesterona -- ReceptorsEsteroidesHormones esteroidesSteroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins on the transcription of the bcl-x gene, where only intragenic progesterone receptor-binding sites (PRbs) were identified. We found that in response to hormone treatment, the PR is recruited to these sites along with two histone acetyltransferases CREB-binding protein (CBP) and GCN5, leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI/SNF complex. Concomitant, a more relaxed chromatin was detected along bcl-x gene mainly in the regions surrounding the intragenic PRbs. PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) elongation activity. Together these events promoted the re-distribution of the active Pol II toward the 3′-end of the gene and a decrease in the ratio between proximal and distal transcription. These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes.Ministerio de Educación y Ciencia (MEC), Spain [BFU2011-28587]; Consejo Nacional de Investigación Científica y Tecnológica [PIP112-200801-00859]; Agencia Nacional de Programación Científica y Tecnológica, [Préstamo BID-PICT2011-1321]; University of Buenos Aires, Argentina. A.R.K.; L.R.V. and A.P. are members of the CONICET-Argentina. G.P.V. is a recipient of the I3 Program. Funding for open access charge: Waived by Oxford University Press.Oxford University Press202320232013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/58299http://dx.doi.org/10.1093/nar/gkt327reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNucleic Acids Research. 2013 Jul 1;41(12):6072-86info:eu-repo/grantAgreement/ES/3PN/BFU2011-28587© The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comhttp://creativecommons.org/licenses/by-nc/3.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/582992026-05-29T05:05:01Z
dc.title.none.fl_str_mv Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
title Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
spellingShingle Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
Bertucci, Paola Y.
Progesterona -- Receptors
Esteroides
Hormones esteroides
title_short Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
title_full Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
title_fullStr Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
title_full_unstemmed Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
title_sort Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation
dc.creator.none.fl_str_mv Bertucci, Paola Y.
Nacht, A. Silvina
Alló, Mariano
Rocha-Viegas, Luciana
Ballaré, Cecilia Julia
Soronellas, Daniel
Castellano, Giancarlo
Zaurín Quer, Roser
Kornblihtt, Alberto R.
Beato, Miguel
Vicent, Guillermo Pablo
Pecci, Adali
author Bertucci, Paola Y.
author_facet Bertucci, Paola Y.
Nacht, A. Silvina
Alló, Mariano
Rocha-Viegas, Luciana
Ballaré, Cecilia Julia
Soronellas, Daniel
Castellano, Giancarlo
Zaurín Quer, Roser
Kornblihtt, Alberto R.
Beato, Miguel
Vicent, Guillermo Pablo
Pecci, Adali
author_role author
author2 Nacht, A. Silvina
Alló, Mariano
Rocha-Viegas, Luciana
Ballaré, Cecilia Julia
Soronellas, Daniel
Castellano, Giancarlo
Zaurín Quer, Roser
Kornblihtt, Alberto R.
Beato, Miguel
Vicent, Guillermo Pablo
Pecci, Adali
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Progesterona -- Receptors
Esteroides
Hormones esteroides
topic Progesterona -- Receptors
Esteroides
Hormones esteroides
description Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins on the transcription of the bcl-x gene, where only intragenic progesterone receptor-binding sites (PRbs) were identified. We found that in response to hormone treatment, the PR is recruited to these sites along with two histone acetyltransferases CREB-binding protein (CBP) and GCN5, leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI/SNF complex. Concomitant, a more relaxed chromatin was detected along bcl-x gene mainly in the regions surrounding the intragenic PRbs. PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) elongation activity. Together these events promoted the re-distribution of the active Pol II toward the 3′-end of the gene and a decrease in the ratio between proximal and distal transcription. These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes.
publishDate 2013
dc.date.none.fl_str_mv 2013
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/58299
http://dx.doi.org/10.1093/nar/gkt327
url http://hdl.handle.net/10230/58299
http://dx.doi.org/10.1093/nar/gkt327
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nucleic Acids Research. 2013 Jul 1;41(12):6072-86
info:eu-repo/grantAgreement/ES/3PN/BFU2011-28587
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
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:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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