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Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era
Glucocorticoids are potent anti-inflammatory drugs that are used to treat an extraordinary range of human disease, including COVID-19, underscoring the ongoing importance of understanding their molecular mechanisms. Early studies of GR signaling led to broad acceptance of models in which glucocortic...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141881/ https://www.ncbi.nlm.nih.gov/pubmed/33891947 http://dx.doi.org/10.1016/j.jbc.2021.100687 |
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author | Gerber, Anthony N. Newton, Robert Sasse, Sarah K. |
author_facet | Gerber, Anthony N. Newton, Robert Sasse, Sarah K. |
author_sort | Gerber, Anthony N. |
collection | PubMed |
description | Glucocorticoids are potent anti-inflammatory drugs that are used to treat an extraordinary range of human disease, including COVID-19, underscoring the ongoing importance of understanding their molecular mechanisms. Early studies of GR signaling led to broad acceptance of models in which glucocorticoid receptor (GR) monomers tether repressively to inflammatory transcription factors, thus abrogating inflammatory gene expression. However, newer data challenge this core concept and present an exciting opportunity to reframe our understanding of GR signaling. Here, we present an alternate, two-part model for transcriptional repression by glucocorticoids. First, widespread GR-mediated induction of transcription results in rapid, primary repression of inflammatory gene transcription and associated enhancers through competition-based mechanisms. Second, a subset of GR-induced genes, including targets that are regulated in coordination with inflammatory transcription factors such as NF-κB, exerts secondary repressive effects on inflammatory gene expression. Within this framework, emerging data indicate that the gene set regulated through the cooperative convergence of GR and NF-κB signaling is central to the broad clinical effectiveness of glucocorticoids in terminating inflammation and promoting tissue repair. |
format | Online Article Text |
id | pubmed-8141881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-81418812021-05-26 Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era Gerber, Anthony N. Newton, Robert Sasse, Sarah K. J Biol Chem JBC Reviews Glucocorticoids are potent anti-inflammatory drugs that are used to treat an extraordinary range of human disease, including COVID-19, underscoring the ongoing importance of understanding their molecular mechanisms. Early studies of GR signaling led to broad acceptance of models in which glucocorticoid receptor (GR) monomers tether repressively to inflammatory transcription factors, thus abrogating inflammatory gene expression. However, newer data challenge this core concept and present an exciting opportunity to reframe our understanding of GR signaling. Here, we present an alternate, two-part model for transcriptional repression by glucocorticoids. First, widespread GR-mediated induction of transcription results in rapid, primary repression of inflammatory gene transcription and associated enhancers through competition-based mechanisms. Second, a subset of GR-induced genes, including targets that are regulated in coordination with inflammatory transcription factors such as NF-κB, exerts secondary repressive effects on inflammatory gene expression. Within this framework, emerging data indicate that the gene set regulated through the cooperative convergence of GR and NF-κB signaling is central to the broad clinical effectiveness of glucocorticoids in terminating inflammation and promoting tissue repair. American Society for Biochemistry and Molecular Biology 2021-04-21 /pmc/articles/PMC8141881/ /pubmed/33891947 http://dx.doi.org/10.1016/j.jbc.2021.100687 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | JBC Reviews Gerber, Anthony N. Newton, Robert Sasse, Sarah K. Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era |
title | Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era |
title_full | Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era |
title_fullStr | Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era |
title_full_unstemmed | Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era |
title_short | Repression of transcription by the glucocorticoid receptor: A parsimonious model for the genomics era |
title_sort | repression of transcription by the glucocorticoid receptor: a parsimonious model for the genomics era |
topic | JBC Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141881/ https://www.ncbi.nlm.nih.gov/pubmed/33891947 http://dx.doi.org/10.1016/j.jbc.2021.100687 |
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