Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy

R Papait, P Cattaneo, P Kunderfranco… - Proceedings of the …, 2013 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
Cardiac hypertrophy, initially an adaptive response of the myocardium to stress, can
progress to heart failure. The epigenetic signature underlying this phenomenon is poorly
understood. Here, we report on the genome-wide distribution of seven histone modifications
in adult mouse cardiomyocytes subjected to a prohypertrophy stimulus in vivo. We found a
set of promoters with an epigenetic pattern that distinguishes specific functional classes of
genes regulated in hypertrophy and identified 9,207 candidate active enhancers whose …
Cardiac hypertrophy, initially an adaptive response of the myocardium to stress, can progress to heart failure. The epigenetic signature underlying this phenomenon is poorly understood. Here, we report on the genome-wide distribution of seven histone modifications in adult mouse cardiomyocytes subjected to a prohypertrophy stimulus in vivo. We found a set of promoters with an epigenetic pattern that distinguishes specific functional classes of genes regulated in hypertrophy and identified 9,207 candidate active enhancers whose activity was modulated. We also analyzed the transcriptional network within which these genetic elements act to orchestrate hypertrophy gene expression, finding a role for myocyte enhancer factor (MEF)2C and MEF2A in regulating enhancers. We propose that the epigenetic landscape is a key determinant of gene expression reprogramming in cardiac hypertrophy and provide a basis for understanding the role of chromatin in regulating this phenomenon.
National Acad Sciences