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Dynamics of chromatin structure in model and pathogenic yeasts


In eukaryotic organisms, essential processes such as RNA transcription, DNA replication and repair are dependent on chromatin structure. Chromatin modifying enzymes are critical for the dynamic regulation of chromatin structure during the cell cycle and the maintenance of proper cell function. The proposal is focused on the Saccharomyces cerevisiae Esa1 protein, a member of the conserved MYST family of histone acetyltransferases. Indeed, Esa1p is involved in very diverse processes such as transcriptional silencing and activation, and have critical roles in DNA damage repair, cell cycle control, and chromosomal and sub-nucleolar architecture. Yet, much remains to be learned about Esa1p genomic targets and interactions.

The aim of this project is to characterize the functional diversity of the MYST HAT Esa1p in DNA-dependent processes. Esa1p is known to regulate activation of transcription through chromatin acteylation within a multimeric complex called NuA4. We will ask whether Esa1p promotes silencing through this complex or another one, yet unidentified. At last, newly defined HAT activities that suppress esa1 mutants will be characterized and their function in DNA damage/repair explored.

The new skills and knowledge acquired during this training in a third country organisation will be transferred and applied to the pathogenic yeast Candida albicans. Indeed, knowledge on chromatin structure function in this species is limited. Most interestingly, various aspects of C. albicans biology are likely to be the subject of epigenetic regulation involving changes in chromatin structure. Thus, we will initiate the functional characterization of the ESA1 homologue in the biology and pathogenesis of C. albicans. This project will allow the applicant to gain a highly qualified training in world-class research institutions and to develop an independent research career.

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