Figure 8. Schematic diagram of the MYH6/7 locus during cardiac development.

At the uninduced locus, the MYH7 and MYH6 promoter regions form a complex with a super-enhancer containing the MYH7-C3 enhancer. The effect of the super-enhancer is depicted as the yellow hue. In early development, this super-enhancer is primarily in contact with the MYH6 promoter, which recruits cardiac transcription factors, chromatin remodelers, and transcription machinery to drive MYH6 expression. During development, activation of the MYH7-C3 region reorganizes the complex and the MYH7 promoter preferentially contacts the regulatory regions. Through competition for transcriptional machinery or through an independent separate mechanism, the MYH6 gene is downregulated. Cells lacking the MYH7-C3 region can established the chromatin structure of the locus but are unable to switch interactions to the MYH7 promoter, causing an upregulation of MYH6 and a downregulation of MYH7. This model highlights the importance of an MYH7 enhancer which is an attractive therapeutic target. TFs, transcription factors.