PT  - JOURNAL ARTICLE
AU  - Ralf Gilsbach
AU  - Martin Schwaderer
AU  - Sebastian Preissl
AU  - Björn A. Grüning
AU  - David Kranzhöfer
AU  - Pedro Schneider
AU  - Thomas G. Nührenberg
AU  - Sonia Mulero-Navarro
AU  - Dieter Weichenhan
AU  - Christian Braun
AU  - Martina Dreßen
AU  - Adam R. Jacobs
AU  - Harald Lahm
AU  - Torsten Doenst
AU  - Rolf Backofen
AU  - Markus Krane
AU  - Bruce D. Gelb
AU  - Lutz Hein
TI  - Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart <em>in vivo</em>
AID  - 10.1101/203075
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 203075
4099  - http://biorxiv.org/content/early/2017/10/16/203075.short
4100  - http://biorxiv.org/content/early/2017/10/16/203075.full
AB  - 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. Thus, the aim of this study was to determine the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. 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.