Polycomb group (PcG) and trithorax group (trxG) genes were discovered in Drosophila melanogaster as repressors and activators of Hox genes, a set of transcription factors that specify the antero-posterior axis of the body plan. PcG and trxG proteins form multimeric complexes that are required to maintain their expression state after the initial transcriptional regulators disappear from the embryo. Subsequent work led to a better understanding of their mechanisms of action. Moreover, PcG and trxG genes have also been identified in vertebrates, where they regulate Hox genes, they are involved in cell proliferation, stem cell identity and cancer, genomic imprinting in plants and mammals and X inactivation. PcG and trxG components form multimeric complexes. Some trxG and PcG components possess methyltransferase activities directed toward specific lysines of histone H3, whereas other trxG and PcG proteins interpret these histone marks. Recent studies have described the genomewide distribution of PcG proteins and of their related histone modification in Drosophila and other species. However, the PcG recruitment code to their target chromatin is still not understood, and the mechanism of PcG-mediated gene silencing is unclear. The formation of subnuclear silencing compartments might contribute to the stable repression of transcription. Drosophila PcG proteins have a speckled nuclear distribution and the number of these so-called PcG bodies is progressively reduced during development. We showed that multiple PREs can associate in the nucleus to enhance the strength of PcG-mediated silencing. However, we do not know how frequent is this clustering process and how important it is functionally at a genomewide level. Our project will tackle these questions by using a combination of genetics, developmental biology, cell biology, genomics and bioinformatic approaches, with the aim to gain an integrated understanding of the role of Polycomb and trithorax in biology