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

Ralf Gilsbach, Martin Schwaderer, Sebastian Preissl, Björn A. Grüning, David Kranzhöfer, Pedro Schneider, Thomas G. Nührenberg, Sonia Mulero-Navarro, Dieter Weichenhan, Christian Braun, Martina Dreßen, Adam R. Jacobs, Harald Lahm, Torsten Doenst, Rolf Backofen, Markus Krane, Bruce D. Gelb and Lutz Hein ()
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Ralf Gilsbach: University of Freiburg
Martin Schwaderer: University of Freiburg
Sebastian Preissl: University of Freiburg
Björn A. Grüning: University of Freiburg
David Kranzhöfer: University of Freiburg
Pedro Schneider: University of Freiburg
Thomas G. Nührenberg: University of Freiburg
Sonia Mulero-Navarro: Icahn School of Medicine at Mount Sinai
Dieter Weichenhan: German Cancer Research Center (DKFZ)
Christian Braun: Ludwig-Maximilians-University
Martina Dreßen: Technische Universität München
Adam R. Jacobs: Icahn School of Medicine at Mount Sinai
Harald Lahm: Technische Universität München
Torsten Doenst: Friedrich-Schiller-University
Rolf Backofen: University of Freiburg
Markus Krane: Technische Universität München
Bruce D. Gelb: Icahn School of Medicine at Mount Sinai
Lutz Hein: University of Freiburg

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02762-z

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