Congrats to Stephan Nothjunge, Thomas Nührenberg, Ralf Gilsbach and many more from the Hein group for their new paper entiteled DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes.
![Distinct DNA methylation patterns in A and B compartments in adult CM. Hi-C contact maps uncover topologically associated domains (TADs) and multi-TAD A/B compartments in adult CM.](/assets/media/nothjunge_2017_natcomm.jpg)
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.