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DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes

2017; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/s41467-017-01724-9

2041-1723

Stephan Nothjunge, Thomas Nührenberg, Björn Grüning, S. Doppler, Sebastian Preißl, Martin Schwaderer, Carolin Rommel, Markus Krane, Lutz Hein, Ralf Gilsbach,

Cancer-related gene regulation

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.