Down-regulation of a male-specific H3K4 demethylase, KDM5D, impairs cardiomyocyte differentiation

Despite the small number of Y chromosome genes, their adequate expression is required for regulation of transcription, translation, and protein stability in males, not only for sex-determination. In addition to their roles in male fertility, Y chromosome has a significant role in development and sexual dimorphism of healthy and disease phenotypes. We observed that KDM5D along with its X-counterpart, KDM5C, are up-regulated during cardiac mesoderm stage of development. Down-regulation of KDM5D using siRNA resulted in accumulation of differentiating cells in S-phase of cell cycle and impaired progression to cardiomyocytes as reflected by altered expression pattern of cardiac progenitor specific markers. Furthermore, while control cells started spontaneous beating at normal physiological range on day 7 of differentiation induction, no spontaneous beating was observed in KDM5D down-regulated cells. Interestingly, the knockdown of KDM5D had no significant effect on the expression level of its X-counterpart, KD...