Format

Send to

Choose Destination
Nat Commun. 2014 Oct 22;5:5288. doi: 10.1038/ncomms6288.

Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease.

Author information

1
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany.
2
1] Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany [2] Hermann Staudinger Graduate School, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany.
3
1] Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany [2] Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg, Hermann-Herder-Strasse 9, 79104 Freiburg, Germany.
4
1] Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany [2] University Heart Center Freiburg/Bad Krozingen, Department of Congenital Heart Defects and Paediatric Cardiology, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
5
1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, Maulbeerstrasse 66, 4058 Basel, Switzerland.
6
European Molecular Biology Laboratory, Genomics Core Facility, Meyerhofstraße 1, 69117 Heidelberg, Germany.
7
Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
8
Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg, Hermann-Herder-Strasse 9, 79104 Freiburg, Germany.
9
Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany.
10
Institute of Physiology I, Life and Brain Center, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
11
1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland [2] University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
12
1] Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany [2] BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestrasse 18, 79104 Freiburg, Germany.

Abstract

The heart is a highly specialized organ with essential function for the organism throughout life. The significance of DNA methylation in shaping the phenotype of the heart remains only partially known. Here we generate and analyse DNA methylomes from highly purified cardiomyocytes of neonatal, adult healthy and adult failing hearts. We identify large genomic regions that are differentially methylated during cardiomyocyte development and maturation. Demethylation of cardiomyocyte gene bodies correlates strongly with increased gene expression. Silencing of demethylated genes is characterized by the polycomb mark H3K27me3 or by DNA methylation. De novo methylation by DNA methyltransferases 3A/B causes repression of fetal cardiac genes, including essential components of the cardiac sarcomere. Failing cardiomyocytes partially resemble neonatal methylation patterns. This study establishes DNA methylation as a highly dynamic process during postnatal growth of cardiomyocytes and their adaptation to pathological stress in a process tightly linked to gene regulation and activity.

PMID:
25335909
PMCID:
PMC4220495
DOI:
10.1038/ncomms6288
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center