DNA binding triggers tetramerization of the glucocorticoid receptor in live cells

Autores
Presman, Diego Martin; Ganguly, Sourav; Schiltz, R. Louis; Johnson, Thomas A.; Karpova, Tatiana S.; Hager, Gordon L.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Transcription factors dynamically bind to chromatin and are essential for the regulation of genes. Although a large percentage of these proteins appear to self-associate to form dimers or higher order oli gomers, t he stoichiometry of DNA-bound transcription factors has been poorly characterized in vivo. The glucocorticoid receptor (GR) is a ligandregulated transcription factor widely believed to act as a dimer or a monomer. Using a unique set of imaging techniques coupled with a cell line containing an array of DNA binding elements, we show that GR is predominantly a tetramer when bound to its target DNA. We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading to tetramerization. We therefore propose that dynamic changes in GR stoichiometry represent a previously unidentified level of regulation in steroid receptor activation. Quaternary structure analysis of other members of the steroid receptor family (estrogen, androgen, and progesterone receptors) reveals variation in oligomerization states among this family of transcription factors. Because GR's oligomerization state has been implicated in therapy outcome, our findings open new doors to the rational design of novel GR ligands and redefine the quaternary structure of steroid receptors.
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Cancer Institute; Estados Unidos
Fil: Ganguly, Sourav. National Cancer Institute; Estados Unidos
Fil: Schiltz, R. Louis. National Cancer Institute; Estados Unidos
Fil: Johnson, Thomas A.. National Cancer Institute; Estados Unidos
Fil: Karpova, Tatiana S.. National Cancer Institute; Estados Unidos
Fil: Hager, Gordon L.. National Cancer Institute; Estados Unidos
Materia
Dimer
Glucocorticoid Receptor
Number And Brightness
Steroid Receptors
Tetramer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/61991
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/61991
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling DNA binding triggers tetramerization of the glucocorticoid receptor in live cellsPresman, Diego MartinGanguly, SouravSchiltz, R. LouisJohnson, Thomas A.Karpova, Tatiana S.Hager, Gordon L.DimerGlucocorticoid ReceptorNumber And BrightnessSteroid ReceptorsTetramerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Transcription factors dynamically bind to chromatin and are essential for the regulation of genes. Although a large percentage of these proteins appear to self-associate to form dimers or higher order oli gomers, t he stoichiometry of DNA-bound transcription factors has been poorly characterized in vivo. The glucocorticoid receptor (GR) is a ligandregulated transcription factor widely believed to act as a dimer or a monomer. Using a unique set of imaging techniques coupled with a cell line containing an array of DNA binding elements, we show that GR is predominantly a tetramer when bound to its target DNA. We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading to tetramerization. We therefore propose that dynamic changes in GR stoichiometry represent a previously unidentified level of regulation in steroid receptor activation. Quaternary structure analysis of other members of the steroid receptor family (estrogen, androgen, and progesterone receptors) reveals variation in oligomerization states among this family of transcription factors. Because GR's oligomerization state has been implicated in therapy outcome, our findings open new doors to the rational design of novel GR ligands and redefine the quaternary structure of steroid receptors.Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Cancer Institute; Estados UnidosFil: Ganguly, Sourav. National Cancer Institute; Estados UnidosFil: Schiltz, R. Louis. National Cancer Institute; Estados UnidosFil: Johnson, Thomas A.. National Cancer Institute; Estados UnidosFil: Karpova, Tatiana S.. National Cancer Institute; Estados UnidosFil: Hager, Gordon L.. National Cancer Institute; Estados UnidosNational Academy of Sciences2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/61991Presman, Diego Martin; Ganguly, Sourav; Schiltz, R. Louis; Johnson, Thomas A.; Karpova, Tatiana S.; et al.; DNA binding triggers tetramerization of the glucocorticoid receptor in live cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 113; 29; 7-2016; 8236-82410027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1606774113info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/113/29/8236info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:44:22Zoai:ri.conicet.gov.ar:11336/61991instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:44:22.324CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
title DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
spellingShingle DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
Presman, Diego Martin
Dimer
Glucocorticoid Receptor
Number And Brightness
Steroid Receptors
Tetramer
title_short DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
title_full DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
title_fullStr DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
title_full_unstemmed DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
title_sort DNA binding triggers tetramerization of the glucocorticoid receptor in live cells
dc.creator.none.fl_str_mv Presman, Diego Martin
Ganguly, Sourav
Schiltz, R. Louis
Johnson, Thomas A.
Karpova, Tatiana S.
Hager, Gordon L.
author Presman, Diego Martin
author_facet Presman, Diego Martin
Ganguly, Sourav
Schiltz, R. Louis
Johnson, Thomas A.
Karpova, Tatiana S.
Hager, Gordon L.
author_role author
author2 Ganguly, Sourav
Schiltz, R. Louis
Johnson, Thomas A.
Karpova, Tatiana S.
Hager, Gordon L.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Dimer
Glucocorticoid Receptor
Number And Brightness
Steroid Receptors
Tetramer
topic Dimer
Glucocorticoid Receptor
Number And Brightness
Steroid Receptors
Tetramer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Transcription factors dynamically bind to chromatin and are essential for the regulation of genes. Although a large percentage of these proteins appear to self-associate to form dimers or higher order oli gomers, t he stoichiometry of DNA-bound transcription factors has been poorly characterized in vivo. The glucocorticoid receptor (GR) is a ligandregulated transcription factor widely believed to act as a dimer or a monomer. Using a unique set of imaging techniques coupled with a cell line containing an array of DNA binding elements, we show that GR is predominantly a tetramer when bound to its target DNA. We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading to tetramerization. We therefore propose that dynamic changes in GR stoichiometry represent a previously unidentified level of regulation in steroid receptor activation. Quaternary structure analysis of other members of the steroid receptor family (estrogen, androgen, and progesterone receptors) reveals variation in oligomerization states among this family of transcription factors. Because GR's oligomerization state has been implicated in therapy outcome, our findings open new doors to the rational design of novel GR ligands and redefine the quaternary structure of steroid receptors.
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Cancer Institute; Estados Unidos
Fil: Ganguly, Sourav. National Cancer Institute; Estados Unidos
Fil: Schiltz, R. Louis. National Cancer Institute; Estados Unidos
Fil: Johnson, Thomas A.. National Cancer Institute; Estados Unidos
Fil: Karpova, Tatiana S.. National Cancer Institute; Estados Unidos
Fil: Hager, Gordon L.. National Cancer Institute; Estados Unidos
description Transcription factors dynamically bind to chromatin and are essential for the regulation of genes. Although a large percentage of these proteins appear to self-associate to form dimers or higher order oli gomers, t he stoichiometry of DNA-bound transcription factors has been poorly characterized in vivo. The glucocorticoid receptor (GR) is a ligandregulated transcription factor widely believed to act as a dimer or a monomer. Using a unique set of imaging techniques coupled with a cell line containing an array of DNA binding elements, we show that GR is predominantly a tetramer when bound to its target DNA. We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading to tetramerization. We therefore propose that dynamic changes in GR stoichiometry represent a previously unidentified level of regulation in steroid receptor activation. Quaternary structure analysis of other members of the steroid receptor family (estrogen, androgen, and progesterone receptors) reveals variation in oligomerization states among this family of transcription factors. Because GR's oligomerization state has been implicated in therapy outcome, our findings open new doors to the rational design of novel GR ligands and redefine the quaternary structure of steroid receptors.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/61991
Presman, Diego Martin; Ganguly, Sourav; Schiltz, R. Louis; Johnson, Thomas A.; Karpova, Tatiana S.; et al.; DNA binding triggers tetramerization of the glucocorticoid receptor in live cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 113; 29; 7-2016; 8236-8241
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/61991
identifier_str_mv Presman, Diego Martin; Ganguly, Sourav; Schiltz, R. Louis; Johnson, Thomas A.; Karpova, Tatiana S.; et al.; DNA binding triggers tetramerization of the glucocorticoid receptor in live cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 113; 29; 7-2016; 8236-8241
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1606774113
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/113/29/8236
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082953734520832
score 13.22299

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