Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION

Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications, and other chromatin features at pathology-associated genes. The extent to which genome-wide chromatin reorganization also contributes to the resultant changes in gene exp...

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Autores: Monte, Emma, Rosa-Garrido, Manuel, Karbassi, Elaheh, Chen, Haodong, Lopez, Rachel, Rau, Christoph D., Wang, Jessica, Nelson, Stanley F., Wu, Yong, Stefani, Enrico, Lusis, Aldons J., Wang, Yibin, Kurdistani, Siavash K., Franklin, Sarah, Vondriska, Thomas M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/414513
Acceso en línea:http://hdl.handle.net/10261/414513
https://api.elsevier.com/content/abstract/scopus_id/84979294546
Access Level:acceso abierto
Palabra clave:Cardiac hypertrophy
Chromatin regulation
Epigenetics
Gene regulation
Heart failure
Ctcf
Hmgb2
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spelling Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATIONMonte, EmmaRosa-Garrido, ManuelKarbassi, ElahehChen, HaodongLopez, RachelRau, Christoph D.Wang, JessicaNelson, Stanley F.Wu, YongStefani, EnricoLusis, Aldons J.Wang, YibinKurdistani, Siavash K.Franklin, SarahVondriska, Thomas M.Cardiac hypertrophyChromatin regulationEpigeneticsGene regulationHeart failureCtcfHmgb2Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications, and other chromatin features at pathology-associated genes. The extent to which genome-wide chromatin reorganization also contributes to the resultant changes in gene expression remains unknown. We examined the roles of two chromatin structural proteins, Ctcf (CCCTC-binding factor) and Hmgb2 (high mobility group protein B2), in regulating pathologic transcription and chromatin remodeling. Our data demonstrate a reciprocal relationship between Hmgb2 and Ctcf in controlling aspects of chromatin structure and gene expression. Both proteins regulate each others' expression as well as transcription in cardiac myocytes; however, only Hmgb2 does so in a manner that involves global reprogramming of chromatin accessibility. We demonstrate that the actions of Hmgb2 on local chromatin accessibility are conserved across genomic loci, whereas the effects on transcription are loci-dependent and emerge in concert with histone modification and other chromatin features. Finally, although both proteins share gene targets, Hmgb2 and Ctcf, neither binds these genes simultaneously nor do they physically colocalize in myocyte nuclei. Our study uncovers a previously unknown relationship between these two ubiquitous chromatin proteins and provides a mechanistic explanation for how Hmgb2 regulates gene expression and cellular phenotype. Furthermore, we provide direct evidence for structural remodeling of chromatin on a genome-wide scale in the setting of cardiac disease.Peer reviewedElsevierAmerican Society for Biochemistry and Molecular Biology202620262016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/414513https://api.elsevier.com/content/abstract/scopus_id/84979294546reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1074/jbc.M116.719633Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4145132026-05-22T06:33:51Z
dc.title.none.fl_str_mv Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
title Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
spellingShingle Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
Monte, Emma
Cardiac hypertrophy
Chromatin regulation
Epigenetics
Gene regulation
Heart failure
Ctcf
Hmgb2
title_short Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
title_full Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
title_fullStr Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
title_full_unstemmed Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
title_sort Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION
dc.creator.none.fl_str_mv Monte, Emma
Rosa-Garrido, Manuel
Karbassi, Elaheh
Chen, Haodong
Lopez, Rachel
Rau, Christoph D.
Wang, Jessica
Nelson, Stanley F.
Wu, Yong
Stefani, Enrico
Lusis, Aldons J.
Wang, Yibin
Kurdistani, Siavash K.
Franklin, Sarah
Vondriska, Thomas M.
author Monte, Emma
author_facet Monte, Emma
Rosa-Garrido, Manuel
Karbassi, Elaheh
Chen, Haodong
Lopez, Rachel
Rau, Christoph D.
Wang, Jessica
Nelson, Stanley F.
Wu, Yong
Stefani, Enrico
Lusis, Aldons J.
Wang, Yibin
Kurdistani, Siavash K.
Franklin, Sarah
Vondriska, Thomas M.
author_role author
author2 Rosa-Garrido, Manuel
Karbassi, Elaheh
Chen, Haodong
Lopez, Rachel
Rau, Christoph D.
Wang, Jessica
Nelson, Stanley F.
Wu, Yong
Stefani, Enrico
Lusis, Aldons J.
Wang, Yibin
Kurdistani, Siavash K.
Franklin, Sarah
Vondriska, Thomas M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cardiac hypertrophy
Chromatin regulation
Epigenetics
Gene regulation
Heart failure
Ctcf
Hmgb2
topic Cardiac hypertrophy
Chromatin regulation
Epigenetics
Gene regulation
Heart failure
Ctcf
Hmgb2
description Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications, and other chromatin features at pathology-associated genes. The extent to which genome-wide chromatin reorganization also contributes to the resultant changes in gene expression remains unknown. We examined the roles of two chromatin structural proteins, Ctcf (CCCTC-binding factor) and Hmgb2 (high mobility group protein B2), in regulating pathologic transcription and chromatin remodeling. Our data demonstrate a reciprocal relationship between Hmgb2 and Ctcf in controlling aspects of chromatin structure and gene expression. Both proteins regulate each others' expression as well as transcription in cardiac myocytes; however, only Hmgb2 does so in a manner that involves global reprogramming of chromatin accessibility. We demonstrate that the actions of Hmgb2 on local chromatin accessibility are conserved across genomic loci, whereas the effects on transcription are loci-dependent and emerge in concert with histone modification and other chromatin features. Finally, although both proteins share gene targets, Hmgb2 and Ctcf, neither binds these genes simultaneously nor do they physically colocalize in myocyte nuclei. Our study uncovers a previously unknown relationship between these two ubiquitous chromatin proteins and provides a mechanistic explanation for how Hmgb2 regulates gene expression and cellular phenotype. Furthermore, we provide direct evidence for structural remodeling of chromatin on a genome-wide scale in the setting of cardiac disease.
publishDate 2016
dc.date.none.fl_str_mv 2016
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/414513
https://api.elsevier.com/content/abstract/scopus_id/84979294546
url http://hdl.handle.net/10261/414513
https://api.elsevier.com/content/abstract/scopus_id/84979294546
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1074/jbc.M116.719633
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv Elsevier
American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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