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Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation
Heterotrimeric G-protein signal transduction initiated by G-protein-coupled receptors (GPCRs) in the plasma membrane is thought to propagate through protein-protein interactions of subunits, Gα and Gβγ in the cytosol. In this study, we show novel nuclear functions of Gβγ through demonstrating intera...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541368/ https://www.ncbi.nlm.nih.gov/pubmed/23326349 http://dx.doi.org/10.1371/journal.pone.0052689 |
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author | Bhatnagar, Anushree Unal, Hamiyet Jagannathan, Rajaganapathi Kaveti, Suma Duan, Zhong-Hui Yong, Sandro Vasanji, Amit Kinter, Michael Desnoyer, Russell Karnik, Sadashiva S. |
author_facet | Bhatnagar, Anushree Unal, Hamiyet Jagannathan, Rajaganapathi Kaveti, Suma Duan, Zhong-Hui Yong, Sandro Vasanji, Amit Kinter, Michael Desnoyer, Russell Karnik, Sadashiva S. |
author_sort | Bhatnagar, Anushree |
collection | PubMed |
description | Heterotrimeric G-protein signal transduction initiated by G-protein-coupled receptors (GPCRs) in the plasma membrane is thought to propagate through protein-protein interactions of subunits, Gα and Gβγ in the cytosol. In this study, we show novel nuclear functions of Gβγ through demonstrating interaction of Gβ(2) with integral components of chromatin and effects of Gβ(2) depletion on global gene expression. Agonist activation of several GPCRs including the angiotensin II type 1 receptor specifically augmented Gβ(2) levels in the nucleus and Gβ(2) interacted with specific nucleosome core histones and transcriptional modulators. Depletion of Gβ(2) repressed the basal and angiotensin II-dependent transcriptional activities of myocyte enhancer factor 2. Gβ(2) interacted with a sequence motif that was present in several transcription factors, whose genome-wide binding accounted for the Gβ(2)-dependent regulation of approximately 2% genes. These findings suggest a wide-ranging mechanism by which direct interaction of Gβγ with specific chromatin bound transcription factors regulates functional gene networks in response to GPCR activation in cells. |
format | Online Article Text |
id | pubmed-3541368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35413682013-01-16 Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation Bhatnagar, Anushree Unal, Hamiyet Jagannathan, Rajaganapathi Kaveti, Suma Duan, Zhong-Hui Yong, Sandro Vasanji, Amit Kinter, Michael Desnoyer, Russell Karnik, Sadashiva S. PLoS One Research Article Heterotrimeric G-protein signal transduction initiated by G-protein-coupled receptors (GPCRs) in the plasma membrane is thought to propagate through protein-protein interactions of subunits, Gα and Gβγ in the cytosol. In this study, we show novel nuclear functions of Gβγ through demonstrating interaction of Gβ(2) with integral components of chromatin and effects of Gβ(2) depletion on global gene expression. Agonist activation of several GPCRs including the angiotensin II type 1 receptor specifically augmented Gβ(2) levels in the nucleus and Gβ(2) interacted with specific nucleosome core histones and transcriptional modulators. Depletion of Gβ(2) repressed the basal and angiotensin II-dependent transcriptional activities of myocyte enhancer factor 2. Gβ(2) interacted with a sequence motif that was present in several transcription factors, whose genome-wide binding accounted for the Gβ(2)-dependent regulation of approximately 2% genes. These findings suggest a wide-ranging mechanism by which direct interaction of Gβγ with specific chromatin bound transcription factors regulates functional gene networks in response to GPCR activation in cells. Public Library of Science 2013-01-09 /pmc/articles/PMC3541368/ /pubmed/23326349 http://dx.doi.org/10.1371/journal.pone.0052689 Text en © 2013 Bhatnagar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bhatnagar, Anushree Unal, Hamiyet Jagannathan, Rajaganapathi Kaveti, Suma Duan, Zhong-Hui Yong, Sandro Vasanji, Amit Kinter, Michael Desnoyer, Russell Karnik, Sadashiva S. Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation |
title | Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation |
title_full | Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation |
title_fullStr | Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation |
title_full_unstemmed | Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation |
title_short | Interaction of G-Protein βγ Complex with Chromatin Modulates GPCR-Dependent Gene Regulation |
title_sort | interaction of g-protein βγ complex with chromatin modulates gpcr-dependent gene regulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541368/ https://www.ncbi.nlm.nih.gov/pubmed/23326349 http://dx.doi.org/10.1371/journal.pone.0052689 |
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