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Epigenetics and chromatin dynamics in gametes : using yeast spores and advanced proteomics

Final Report Summary - EPIGAM2 (Epigenetics and chromatin dynamics in gametes : using yeast spores and advanced proteomics)

This program aimed that finalizing the training and facilitating the installation of the group of the researcher Jerome Govin. His research program is dedicated to the understanding of the organization of DNA inside the cell nucleus, and more particularly in gametes.
Indeed, gametes are crucial cells, essential for the survival of mammals, as well as other animals, plants, fungi and even lower eukaryotes. However, their nuclear organization remains poorly understood. Filling this gap in our knowledge is one of the main challenges of biology today. In humans, sperm DNA has a specific chromatin structure, which is essential for fertilization. But beyond fertility, deciphering how chromatin is organized in gametes gives rise to new concepts, reaching out to many fields.

This research program deciphers chromatin dynamics during the differentiation of male gametes.

The study of gametes in higher eukaryotes is limited by the technical methods available, which are often expensive and time-consuming. We previously revealed that a simple yeast spore model shares functional epigenetic similarities with mammalian sperm. This makes yeast spores a unique and powerful model to study gametes and the organization of their chromatin.

This basic research program implements ambitious exploratory approaches combining structural biology, genetics, biochemistry and proteomics. More precisely, the general objective of this program is to perform a comprehensive characterization of a chromatin factor essential for sporulation and gametogenesis.

More precisely, the general objective of this program is to perform a comprehensive characterization of the factor Bdf1 during the sporulation of the yeast S. cerevisiae. Bdf1 is a member of the BET protein family, Mammalian members of this family, such as Brdt, are essential for the post-meiotic differentiation of sperm. BET proteins are major chromatin-associated factors involved in transcription regulation. They are essential elements of chromatin signaling pathways, and play an important role during gametogenesis. Thus, the yeast BET protein Bdf1 is essential for sporulation, but its role in this process is unclear.

We have previously shown that Bdf1 is highly expressed in spores, and recognizes acetylated H4. Its pattern of expression during sporulation is very interesting because the increase of Bdf1 levels correlate with a hyperacetylation of H4 observed in spores (Govin J et al. Genes Dev 2010). Here, this protein has been characterized in in vitro using biochemical and structural approaches, and in vivo using genetic and biochemical approaches. We show that specific domains of this protein regulates master regulators of the sporulation program.

Moreover, this program lead to the development of a new translational program. It is focused on the treatment of pathogenic yeasts infections. This program currently represents >50% of the activity of my group. It is funded by several agencies, including French National Research Agency (ANR) and NIH (USA).

Finally, the researcher has been able to create and consolidate his group. He started in 2012 with a permanent position funded by Inserm and also created his research group at that time. Additional funding has been provided by the French National Research Agency and this Marie Curie Action. It is now composed of one post doc, two PhD student, one lab manager and two technicians.