Jumonji represses α-cardiac myosin heavy chain expression via inhibiting MEF2 activity

Expression of α-cardiac myosin heavy chain gene (αMHC) is developmentally regulated in normal embryonic hearts and down-regulated in cardiac myopathy and failing hearts. Jumonji (JMJ) has been shown to be critical for normal cardiovascular development and functions as a transcriptional repressor. Here, we demonstrate that JMJ represses αMHC expression through inhibition of myocyte enhancer factor 2 (MEF2) activity. In primary cardiomyocytes, overexpression of JMJ leads to marked reduction of endogenous αMHC expression. JMJ represses the synergistic activation of αMHC by MEF2 and thyroid hormone receptor (TR). Interestingly, JMJ inhibits transcriptional activities of all MEF2 isoforms, but not the TR-dependent activation. The transcriptional repression domain of JMJ interacts with the N-terminal part of MEF2A, resulting in the repression of MEF2A activities. These results suggest that JMJ represses αMHC expression via protein–protein interaction with MEF2A.