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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/175223
Ver los metadatos del registro completo
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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/ |
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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 |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.13397 |