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Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease

Author

Listed:
  • Ralf Gilsbach

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg)

  • Sebastian Preissl

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg
    Hermann Staudinger Graduate School, University of Freiburg)

  • Björn A. Grüning

    (Bioinformatics Group, University of Freiburg
    Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg)

  • Tilman Schnick

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg
    University Heart Center Freiburg/Bad Krozingen, University of Freiburg)

  • Lukas Burger

    (Friedrich Miescher Institute for Biomedical Research
    Swiss Institute of Bioinformatics)

  • Vladimir Benes

    (European Molecular Biology Laboratory, Genomics Core Facility)

  • Andreas Würch

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Ulrike Bönisch

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Stefan Günther

    (Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, University of Freiburg)

  • Rolf Backofen

    (Bioinformatics Group, University of Freiburg)

  • Bernd K. Fleischmann

    (Institute of Physiology I, Life and Brain Center, University of Bonn)

  • Dirk Schübeler

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Lutz Hein

    (Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg
    BIOSS Centre for Biological Signalling Studies, University of Freiburg)

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.

Suggested Citation

  • Ralf Gilsbach & Sebastian Preissl & Björn A. Grüning & Tilman Schnick & Lukas Burger & Vladimir Benes & Andreas Würch & Ulrike Bönisch & Stefan Günther & Rolf Backofen & Bernd K. Fleischmann & Dirk Sc, 2014. "Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6288
    DOI: 10.1038/ncomms6288
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    Cited by:

    1. Cornelis J. Boogerd & Ilaria Perini & Eirini Kyriakopoulou & Su Ji Han & Phit La & Britt Swaan & Jari B. Berkhout & Danielle Versteeg & Jantine Monshouwer-Kloots & Eva Rooij, 2023. "Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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