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Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo

Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation, and in disease remains unknown. Here, we investi...

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Autores principales: Gilsbach, Ralf, Schwaderer, Martin, Preissl, Sebastian, Grüning, Björn A., Kranzhöfer, David, Schneider, Pedro, Nührenberg, Thomas G., Mulero-Navarro, Sonia, Weichenhan, Dieter, Braun, Christian, Dreßen, Martina, Jacobs, Adam R., Lahm, Harald, Doenst, Torsten, Backofen, Rolf, Krane, Markus, Gelb, Bruce D., Hein, Lutz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786002/
https://www.ncbi.nlm.nih.gov/pubmed/29374152
http://dx.doi.org/10.1038/s41467-017-02762-z
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author Gilsbach, Ralf
Schwaderer, Martin
Preissl, Sebastian
Grüning, Björn A.
Kranzhöfer, David
Schneider, Pedro
Nührenberg, Thomas G.
Mulero-Navarro, Sonia
Weichenhan, Dieter
Braun, Christian
Dreßen, Martina
Jacobs, Adam R.
Lahm, Harald
Doenst, Torsten
Backofen, Rolf
Krane, Markus
Gelb, Bruce D.
Hein, Lutz
author_facet Gilsbach, Ralf
Schwaderer, Martin
Preissl, Sebastian
Grüning, Björn A.
Kranzhöfer, David
Schneider, Pedro
Nührenberg, Thomas G.
Mulero-Navarro, Sonia
Weichenhan, Dieter
Braun, Christian
Dreßen, Martina
Jacobs, Adam R.
Lahm, Harald
Doenst, Torsten
Backofen, Rolf
Krane, Markus
Gelb, Bruce D.
Hein, Lutz
author_sort Gilsbach, Ralf
collection PubMed
description Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation, and in disease remains unknown. Here, we investigate the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. We find that prenatal development and postnatal maturation are characterized by a cooperation of active CpG methylation and histone marks at cis-regulatory and genic regions to shape the cardiac myocyte transcriptome. In contrast, pathological gene expression in terminal heart failure is accompanied by changes in active histone marks without major alterations in CpG methylation and repressive chromatin marks. Notably, cis-regulatory regions in cardiac myocytes are significantly enriched for cardiovascular disease-associated variants. This study uncovers distinct layers of epigenetic regulation not only during prenatal development and postnatal maturation but also in diseased human cardiac myocytes.
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spelling pubmed-57860022018-01-29 Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo Gilsbach, Ralf Schwaderer, Martin Preissl, Sebastian Grüning, Björn A. Kranzhöfer, David Schneider, Pedro Nührenberg, Thomas G. Mulero-Navarro, Sonia Weichenhan, Dieter Braun, Christian Dreßen, Martina Jacobs, Adam R. Lahm, Harald Doenst, Torsten Backofen, Rolf Krane, Markus Gelb, Bruce D. Hein, Lutz Nat Commun Article Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation, and in disease remains unknown. Here, we investigate the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. We find that prenatal development and postnatal maturation are characterized by a cooperation of active CpG methylation and histone marks at cis-regulatory and genic regions to shape the cardiac myocyte transcriptome. In contrast, pathological gene expression in terminal heart failure is accompanied by changes in active histone marks without major alterations in CpG methylation and repressive chromatin marks. Notably, cis-regulatory regions in cardiac myocytes are significantly enriched for cardiovascular disease-associated variants. This study uncovers distinct layers of epigenetic regulation not only during prenatal development and postnatal maturation but also in diseased human cardiac myocytes. Nature Publishing Group UK 2018-01-26 /pmc/articles/PMC5786002/ /pubmed/29374152 http://dx.doi.org/10.1038/s41467-017-02762-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gilsbach, Ralf
Schwaderer, Martin
Preissl, Sebastian
Grüning, Björn A.
Kranzhöfer, David
Schneider, Pedro
Nührenberg, Thomas G.
Mulero-Navarro, Sonia
Weichenhan, Dieter
Braun, Christian
Dreßen, Martina
Jacobs, Adam R.
Lahm, Harald
Doenst, Torsten
Backofen, Rolf
Krane, Markus
Gelb, Bruce D.
Hein, Lutz
Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
title Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
title_full Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
title_fullStr Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
title_full_unstemmed Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
title_short Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
title_sort distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786002/
https://www.ncbi.nlm.nih.gov/pubmed/29374152
http://dx.doi.org/10.1038/s41467-017-02762-z
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