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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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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. |
format | Online Article Text |
id | pubmed-5786002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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