Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors.

ABSTRACT: Cardiomyocytes acquire their primary specialized function (contraction) before exiting the cell cycle. In this regard, proliferation and differentiation must be precisely coordinated for proper cardiac morphogenesis. Here, we have investigated the complex transcriptional mechanisms employed by cardiomyocytes to coordinate antagonistic cell-cycle and differentiation gene programs through the molecular dissection of the core cardiac transcription factor, MEF2. Knockdown of individual MEF2 proteins, MEF2A, -C, and -D, in primary neonatal cardiomyocytes resulted in radically distinct and opposite effects on cellular homeostasis and gene regulation. MEF2A and MEF2D were absolutely required for cardiomyocyte survival, whereas MEF2C, despite its major role in cardiac morphogenesis and direct repr

SUBMITTER: Desjardins CA 

PROVIDER: S-EPMC5481567 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature