Translational epigenetics : from baker’s to pathogenic yeasts

Orateur : Jérôme GOVIN (Biosciences and Biotechnology Institute of Grenoble, France)

Our recent scientific journey started with the exploration of chromatin signaling pathways in the baker’s yeast, Saccharomyces cerevisiae. In many organisms, including yeast and mammals, bromodomain-containing proteins of the BET family are essential for the regulation of transcription. In mammals, the testisspecific BET member, Brdt, has been shown to be important for sperm production. In yeasts, the differentiation of spores shares striking similarities with mammalian spermatogenesis. We will present how the yeast BET protein Bdf1 is essential for sporulation, the control of its transcription program and the establishment of the chromatin organization in spores. Our scientific journey continues with a biomedical translation of this fundamental work. The BET member Bdf1 was identified as an interesting new therapeutic target to treat patients with yeast infections. Indeed, invasive fungal infections are a major cause of mortality and new anti-fungal drugs are urgently needed. We show that Bdf1 is essential for Candida albicans, a widespread fungal pathogen. Mutating its bromodomains resulted in a loss of viability in vitro and decreased virulence in mice. Small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human bromodomains were identified and active against yeast growth. This translational research program identifies Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET functions.

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