Final Report Summary - REPODDID (Regulation of Polycomb Complex (PRC2) during development and in diseases) The development of multicellular organisms entails the precise orchestration of gene expression profiles. The Polycomb machinery has an essential function during this process since it is required for the proper maintenance of gene silencing. Its activity is supposed to rely on its capacity to modify the structure of chromatin in order to prevent aberrant gene activation. While the study of the Polycomb machinery has retained lots of attention, many aspect of its regulation remain unclear. We have tackled this question through different angles. We have uncovered new factors that regulate PRC2 (a key complex of the Polycomb machinery) activity and we are currently investigating the underlying molecular mechanism. We have studied the role that long non-coding RNA could play in the targeting PRC2 to chromatin. Our recently published study, together with other publications, prompts for the re-evaluation of this model. Alterations of the Polycomb machinery are frequent in cancer however there exact contribution is still enigmatic. We showed that the apparent overexpression of components of the PRC2 complex is rather a consequence than a cause of tumor progression. Finally, we have studied the enzymatic activity of PRC2 and uncovered new substrate for this complex.
