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

Anna Meyfour, Sara Pahlavan, Hassan Ansari, Hossein Baharvand*, Ghasem Hosseini Salekdeh

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)


    Despite the small number of Y chromosome genes, their adequate expression is required for regulation of transcription, translation, and protein stability in males, not just for sex determination. In addition to the role in male fertility, the Y chromosome has a significant role in the development and sexual dimorphism of healthy and disease phenotypes. We observed that KDM5D along with its X-counterpart, KDM5C, are up-regulated during the cardiac mesoderm stage of development. Down-regulation of KDM5D using siRNA resulted in accumulation of differentiating cells in the S-phase of the cell cycle and impaired progression to cardiomyocytes as reflected by an altered expression pattern of cardiac progenitor specific markers. Furthermore, while control cells started spontaneous beating at a 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, KDM5C. Thus, we suggest that KDM5D, in cooperation with its X homologue as a dose-sensitive gene, may have an important role in cardiomyocyte differentiation. Our study presents further evidence on the contribution of Y chromosome genes to sex-dependent development outside of sex determination.

    Original languageEnglish
    Pages (from-to)4277-4282
    Number of pages6
    JournalJournal of Proteome Research
    Issue number12
    Early online date27 Sep 2019
    Publication statusPublished - 6 Dec 2019


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