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Figure 8


Fig. 8. Mechanistic model. HDAC activity negatively regulates the entry of mesoderm cells into the cardiac-muscle lineage. Relief of HDAC inhibition by TSA, CaMK or, possibly, DMSO enhances the differentiation of P19 stem cells into cardiomyocytes, whereas the overexpression of HDAC4 inhibits differentiation (bold, black). Thus, HDAC activity inhibits mesoderm cells from entering the cardiac lineage and upregulating the expression of Nkx2-5, Gata4 and Mef2c. Furthermore, the overexpression of the dominant-negative MEF2C/EnR enhances cardiomyogenensis, by possibly disrupting HDAC activity, allowing more cells into the cardiac lineage. Similarly, MEF2C/EnR expressed in cardiomyoblasts displays an initial enhancement of the cardiac factors; however, MEF2C/EnR in these cells (asterisk) results in the subsequent downregulation of this positive loop and inhibition of cardiomyogenesis (Karamboulas et al., 2006).





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