DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes

Stephan Nothjunge, Thomas G. Nührenberg, Björn A. Grüning, Stefanie A. Doppler, Sebastian Preissl, Martin Schwaderer, Carolin Rommel, Markus Krane, Lutz Hein and Ralf Gilsbach ()
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Stephan Nothjunge: Faculty of Medicine, University of Freiburg
Thomas G. Nührenberg: Faculty of Medicine, University of Freiburg
Björn A. Grüning: Department of Computer Science, University of Freiburg
Stefanie A. Doppler: Division of Experimental Surgery, German Heart Center
Sebastian Preissl: Faculty of Medicine, University of Freiburg
Martin Schwaderer: Faculty of Medicine, University of Freiburg
Carolin Rommel: Faculty of Medicine, University of Freiburg
Markus Krane: Division of Experimental Surgery, German Heart Center
Lutz Hein: Faculty of Medicine, University of Freiburg
Ralf Gilsbach: Faculty of Medicine, University of Freiburg

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Storage of chromatin in restricted nuclear space requires dense packing while ensuring DNA accessibility. Thus, different layers of chromatin organization and epigenetic control mechanisms exist. Genome-wide chromatin interaction maps revealed large interaction domains (TADs) and higher order A and B compartments, reflecting active and inactive chromatin, respectively. The mutual dependencies between chromatin organization and patterns of epigenetic marks, including DNA methylation, remain poorly understood. Here, we demonstrate that establishment of A/B compartments precedes and defines DNA methylation signatures during differentiation and maturation of cardiac myocytes. Remarkably, dynamic CpG and non-CpG methylation in cardiac myocytes is confined to A compartments. Furthermore, genetic ablation or reduction of DNA methylation in embryonic stem cells or cardiac myocytes, respectively, does not alter genome-wide chromatin organization. Thus, DNA methylation appears to be established in preformed chromatin compartments and may be dispensable for the formation of higher order chromatin organization.

Date: 2017
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DOI: 10.1038/s41467-017-01724-9

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