Fig. 5. Mechanistic model for the effect of MEF2 disruption on the differentiation of cells into cardiac muscle. In the cardiomyoblast, MEF2C, GATA4 and Nkx2-5 are important for the maintenance of the cardiomyoblast phenotype and for subsequent differentiation into cardiomyocytes (Dodou et al., 2004; Grepin et al., 1997; Jamali et al., 2001; Reecy et al., 1999; Searcy et al., 1998; Skerjanc et al., 1998). The presence of MEF2C/EnR downregulated the expression of genes encoding Nkx2-5, MEF2C and GATA4, and inhibited the progression of cardiomyoblasts into cardiomyocytes. An initial enhancement of Nkx2-5 and MEF2C in the stem/mesoderm cell confirmed previous results showing an increase in Nkx2-5 and Gata4 expression, probably due to the relief of HDAC inhibition of cardiomyoblast formation by MEF2C/EnR (Karamboulas et al., 2006).