Our developmental studies provide an insight into the pathogenesis of heart failure in adults. These studies reveal a mechanistic link between fetal cardiomyocytes and pathologically stressed adult cardiomyocytes at the level of chromatin regulation. In embryos, chromatin-regulating factors within the cardiomyocytes respond to developmental signals to program cardiac gene expression to promote cell proliferation and inhibit premature cell differentiation. In the neonatal period, the activity of these developmental chromatin regulators is quickly turned off in cardiomyocytes, coinciding with the cessation of cell proliferation and advance in cell differentiation toward adult maturity. When the mature hearts are pathologically stressed, those chromatin regulators essential for cardiomyocyte development in embryos are reactivated, triggering gene reprogramming to a fetal-like state and pathological cardiac hypertrophy. Furthermore, in the study of chromatin regulation and cardiac gene expression, we identified a long noncoding RNA that interacts with chromatin remodeling factor to regulate the cardiac response to environmental changes. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
Keywords: BAF; Brg1; Chromatin; Development; Gene expression; Heart failure; Hypertrophy; Mhrt; Myheart.
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