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Nat Commun. 2018 Jan 26;9(1):391. doi: 10.1038/s41467-017-02762-z.

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

Author information

1
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.
2
Bioinformatics Group, Department of Computer Science, University of Freiburg, 79110, Freiburg, Germany.
3
Department for Cardiology und Angiology II, University Heart Center Freiburg • Bad Krozingen, 79189, Bad Krozingen, Germany.
4
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6542, USA.
5
Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
6
Forensic Institute, Ludwig-Maximilians-University, 80046, Munich, Germany.
7
Department of Cardiovascular Surgery, German Heart Center, Technische Universität München, 80636, Munich, Germany.
8
Insure (Institute for Translational Cardiac Surgery), Department of Cardiovascular Surgery, German Heart Center, Technische Universität München, 80636, Munich, Germany.
9
Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
10
Department of Cardiothoracic Surgery, Jena University Hospital, Friedrich-Schiller-University, 07740, Jena, Germany.
11
DZHK (German Center for Cardiovascular Research) - Partner Site Munich Heart Alliance, Munich, 60046, Germany.
12
Department of Genetics and Genomic Sciences & Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA.
13
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany. lutz.hein@pharmakol.uni-freiburg.de.
14
BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104, Freiburg, Germany. lutz.hein@pharmakol.uni-freiburg.de.

Abstract

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.

PMID:
29374152
PMCID:
PMC5786002
DOI:
10.1038/s41467-017-02762-z
[Indexed for MEDLINE]
Free PMC Article

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