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The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart
The Polycomb-group protein, Ezh2, is required for epigenetic gene silencing in the adult heart by unknown mechanism. We investigated the role of Ezh2 and non-coding RNAs in a mouse model of pressure overload using transverse aortic constriction (TAC) attenuated by the prototypical histone deacetylas...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902903/ https://www.ncbi.nlm.nih.gov/pubmed/24137001 http://dx.doi.org/10.1093/nar/gkt896 |
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author | Mathiyalagan, Prabhu Okabe, Jun Chang, Lisa Su, Yidan Du, Xiao-Jun El-Osta, Assam |
author_facet | Mathiyalagan, Prabhu Okabe, Jun Chang, Lisa Su, Yidan Du, Xiao-Jun El-Osta, Assam |
author_sort | Mathiyalagan, Prabhu |
collection | PubMed |
description | The Polycomb-group protein, Ezh2, is required for epigenetic gene silencing in the adult heart by unknown mechanism. We investigated the role of Ezh2 and non-coding RNAs in a mouse model of pressure overload using transverse aortic constriction (TAC) attenuated by the prototypical histone deacetylase inhibitor, trichostatin A (TSA). Chromatin immunoprecipitation of TAC and TAC+TSA hearts suggests interaction of Ezh2 and primary microRNA-208b (pri-miR-208b) in the regulation of hypertrophic gene expression. RNAi silencing of pri-miR-208b and Ezh2 validate pri-miR-208b-mediated transcriptional silencing of genes implicated in cardiac hypertrophy including the suppression of the bi-directional promoter (bdP) of the cardiac myosin heavy chain genes. In TAC mouse heart, TSA attenuated Ezh2 binding to bdP and restored antisense β-MHC and α-MHC gene expression. RNA-chromatin immunoprecipitation experiments in TAC hearts also show increased pri-miR-208b dependent-chromatin binding. These results are the first description by which primary miR interactions serve to integrate chromatin modifications and the transcriptional response to distinct signaling cues in the heart. These studies provide a framework for MHC expression and regulation of genes implicated in pathological remodeling of ventricular hypertrophy. |
format | Online Article Text |
id | pubmed-3902903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-39029032014-01-27 The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart Mathiyalagan, Prabhu Okabe, Jun Chang, Lisa Su, Yidan Du, Xiao-Jun El-Osta, Assam Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics The Polycomb-group protein, Ezh2, is required for epigenetic gene silencing in the adult heart by unknown mechanism. We investigated the role of Ezh2 and non-coding RNAs in a mouse model of pressure overload using transverse aortic constriction (TAC) attenuated by the prototypical histone deacetylase inhibitor, trichostatin A (TSA). Chromatin immunoprecipitation of TAC and TAC+TSA hearts suggests interaction of Ezh2 and primary microRNA-208b (pri-miR-208b) in the regulation of hypertrophic gene expression. RNAi silencing of pri-miR-208b and Ezh2 validate pri-miR-208b-mediated transcriptional silencing of genes implicated in cardiac hypertrophy including the suppression of the bi-directional promoter (bdP) of the cardiac myosin heavy chain genes. In TAC mouse heart, TSA attenuated Ezh2 binding to bdP and restored antisense β-MHC and α-MHC gene expression. RNA-chromatin immunoprecipitation experiments in TAC hearts also show increased pri-miR-208b dependent-chromatin binding. These results are the first description by which primary miR interactions serve to integrate chromatin modifications and the transcriptional response to distinct signaling cues in the heart. These studies provide a framework for MHC expression and regulation of genes implicated in pathological remodeling of ventricular hypertrophy. Oxford University Press 2014-01 2013-10-09 /pmc/articles/PMC3902903/ /pubmed/24137001 http://dx.doi.org/10.1093/nar/gkt896 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Mathiyalagan, Prabhu Okabe, Jun Chang, Lisa Su, Yidan Du, Xiao-Jun El-Osta, Assam The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart |
title | The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart |
title_full | The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart |
title_fullStr | The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart |
title_full_unstemmed | The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart |
title_short | The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart |
title_sort | primary microrna-208b interacts with polycomb-group protein, ezh2, to regulate gene expression in the heart |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902903/ https://www.ncbi.nlm.nih.gov/pubmed/24137001 http://dx.doi.org/10.1093/nar/gkt896 |
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