Abstract
Epigenetic mechanisms are essential for cardiomyocyte function and adaptation in development, postnatal growth, and during cardiac remodeling in heart failure. Recent advances in the identification of cell-type-specific markers have facilitated the development of techniques to purify cardiomyocytes and their nuclei from intact heart tissue and to study DNA methylation and posttranslational histone modifications on a genome-wide basis. Cardiomyocyte development and postnatal maturation were accompanied by DNA demethylation of gene bodies of sarcomeric genes until adulthood. Genes that are expressed during the fetal period were also demethylated but were postnatally repressed by trimethylation of histone 3 at lysine 27 (developmental genes) or by de novo DNA methylation mediated by DNA methyltransferases 3A/3B (fetal sarcomeric genes). Dynamic changes in DNA methylation and histone modifications can be recognized by specialized “reader” proteins which modulate cardiomyocyte function. Future studies will be important to unravel the complex interplay between epigenetic modifications of DNA and histones and to identify the involved signaling pathways.
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This work was supported by the Deutsche Forschungsgemeinschaft SFB 992 (Medical Epigenetics, project B03) and the BIOSS Centre for Biological Signalling Studies.
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Hein, L. (2016). Epigenome Dynamics and Reader Proteins in Cardiomyocyte Development and Heart Failure. In: Backs, J., McKinsey, T.A. (eds) Epigenetics in Cardiac Disease. Cardiac and Vascular Biology, vol 1. Springer, Cham. https://doi.org/10.1007/978-3-319-41457-7_2
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