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The role of phase separation in epigenetic inheritance by Polycomb Group proteins.


University of Montreal

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Dr Nicole Francis Applications accepted all year round Funded PhD Project (Students Worldwide)

About the Project

In recent years, the role of phase separation in organizing macromolecules in cells is increasingly appreciated. This includes the organization of chromatin into physical and functional domains. We are studying how Polycomb Group proteins can mediate phase separation with chromatin, how this is modulated by histone modifications. We and others have found that a Sterile Alpha Motif (SAM) in Polyhomeotic, which can form polymers, is important for organizing PcG proteins into clusters and large “bodies” in cells. Ph SAM is also important for repression of gene expression and long range chromatin interactions. The Ph SAM, in conjunction with other sequences in Ph, forms phase separated condensates with chromatin in vitro. In vivo, formation of PcG foci depends on the SAM, and these foci are regulated through the cell cycle. The project involves dissecting the mechanism of phase separation mediated by Ph, determining the role of Ph SAM-dependent phase separation in vivo, determining how phase separation may occur in the context of PRC1, understanding the interplay between histone modifications and phase separation, and how phase separation may be important for propagation of epigenetic information through the cell cycle.
The project involves genome engineering in Drosophila tissue culture cells, in vivo analysis of chromatin (microscopy and molecular biology-based methods like ChIP and 3C), and in vitro biochemical reconstitution (protein purification, biochemical and microscopy based analysis).
Background in molecular biology and biochemistry or biophysics is highly recommended, but the most important characteristics are motivation, ability to work independently, and willingness to learn. We would also welcome students with more theoretical or computational backgrounds.

References

Wani, A.H.*, Boettiger, A.N.*, Schorderet, P., Ergun, A., Munger, C., Sadreyev, R.I., Zhuang, X., Kingston, R.E., and Francis, N.J. (2016) Chromatin topology is coupled to Polycomb group protein subnuclear organization. Nat. Commun. 13:10291 PMID 26759081
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