Cavalli Lab Profile

Research Focus: Polycomb, the Cell Nucleus and the Regulation of Genome Function

Polycomb Group (PcG) and trithorax Group (trxG) genes are responsible for the maintenance of the regulatory states of homeotic and other developmental genes. PcG and trxG proteins are chromatin factors that maintain, respectively, repressed and active transcriptional states of their targets by binding to DNA sequences known as Polycomb- and trithorax response elements (PREs and TREs). These elements are able to transmit the memory of chromatin states through cell division by imposing epigenetic marks on their target chromatin and by regulating nuclear compartmentalization of their target genes. We would like to understand how PcG and trxG complexes are recruited at PREs and TREs; what are the molecular mechanisms that enable chromatin inheritance through cell division and how PcG and trxG proteins affect chromosome architecture and the three-dimensional organisation of the cell nucleus.

Our past research has revealed that a regulatory element of a homeotic gene, named Fab-7, is capable of efficiently transmitting the epigenetic inheritance of both active and repressed chromatin states in a trxG- and PcG-dependent manner. Moreover, the transmission of cell memory by this element brings into play long-distance chromosomal interactions in the cell nucleus. We now wish to dissect these phenomena by using our expertise in a variety of genetic, cellular and molecular biology approaches, using Drosophila as a model system.