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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...

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Autores principales: Mathiyalagan, Prabhu, Okabe, Jun, Chang, Lisa, Su, Yidan, Du, Xiao-Jun, El-Osta, Assam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
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.
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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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