Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms

Autores
Johnson, Thomas A.; Paakinaho, Ville; Kim, Sohyoung; Hager, Gordon L.; Presman, Diego Martin
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.
Fil: Johnson, Thomas A.. National Institutes of Health; Estados Unidos
Fil: Paakinaho, Ville. University Of Eastern Finland.; Finlandia
Fil: Kim, Sohyoung. National Institutes of Health; Estados Unidos
Fil: Hager, Gordon L.. National Institutes of Health; Estados Unidos
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Materia
GLUCOCORTICOID RECEPTOR
DIMER
MONOMER
CHROMATIN BINDING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/175223

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network_name_str CONICET Digital (CONICET)
spelling Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric formsJohnson, Thomas A.Paakinaho, VilleKim, SohyoungHager, Gordon L.Presman, Diego MartinGLUCOCORTICOID RECEPTORDIMERMONOMERCHROMATIN BINDINGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.Fil: Johnson, Thomas A.. National Institutes of Health; Estados UnidosFil: Paakinaho, Ville. University Of Eastern Finland.; FinlandiaFil: Kim, Sohyoung. National Institutes of Health; Estados UnidosFil: Hager, Gordon L.. National Institutes of Health; Estados UnidosFil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaNature2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/175223Johnson, Thomas A.; Paakinaho, Ville; Kim, Sohyoung; Hager, Gordon L.; Presman, Diego Martin; Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms; Nature; Nature Communications; 12; 1; 12-2021; 1-142041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-021-22234-9info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-22234-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:45Zoai:ri.conicet.gov.ar:11336/175223instacron: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:34982025-09-03 09:47:45.499CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
title Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
spellingShingle Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
Johnson, Thomas A.
GLUCOCORTICOID RECEPTOR
DIMER
MONOMER
CHROMATIN BINDING
title_short Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
title_full Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
title_fullStr Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
title_full_unstemmed Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
title_sort Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
dc.creator.none.fl_str_mv Johnson, Thomas A.
Paakinaho, Ville
Kim, Sohyoung
Hager, Gordon L.
Presman, Diego Martin
author Johnson, Thomas A.
author_facet Johnson, Thomas A.
Paakinaho, Ville
Kim, Sohyoung
Hager, Gordon L.
Presman, Diego Martin
author_role author
author2 Paakinaho, Ville
Kim, Sohyoung
Hager, Gordon L.
Presman, Diego Martin
author2_role author
author
author
author
dc.subject.none.fl_str_mv GLUCOCORTICOID RECEPTOR
DIMER
MONOMER
CHROMATIN BINDING
topic GLUCOCORTICOID RECEPTOR
DIMER
MONOMER
CHROMATIN BINDING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.
Fil: Johnson, Thomas A.. National Institutes of Health; Estados Unidos
Fil: Paakinaho, Ville. University Of Eastern Finland.; Finlandia
Fil: Kim, Sohyoung. National Institutes of Health; Estados Unidos
Fil: Hager, Gordon L.. National Institutes of Health; Estados Unidos
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
description A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
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/11336/175223
Johnson, Thomas A.; Paakinaho, Ville; Kim, Sohyoung; Hager, Gordon L.; Presman, Diego Martin; Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms; Nature; Nature Communications; 12; 1; 12-2021; 1-14
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/175223
identifier_str_mv Johnson, Thomas A.; Paakinaho, Ville; Kim, Sohyoung; Hager, Gordon L.; Presman, Diego Martin; Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms; Nature; Nature Communications; 12; 1; 12-2021; 1-14
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-021-22234-9
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-22234-9
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
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
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