POLYCOMB AND TRITHORAX GROUP PROTEINS AND MECHANISMS OF MAINTENANCE OF CELL IDENTITY

The possibility of correcting genetic defects of higher organisms by genetic tools (eg cell transplantation and gene transfer technologies), is one of the most appealing tracks that biological sciences may be pursuing. This implies a complete comprehension of how cell identity is acquired and maintained during development and differentiation. The Polycomb-group (PcG) and trithorax-group (trxG) genes encode for evolutionary conserved chromosomal proteins that control cell identity. In Drosophila, PcG and trxG proteins are part of a "cellular memory" mechanism acting on specialized DNA elements (PREs) that fix determined states on developmentally regulated genes and convey epigenetic inheritance. However, to date the mechanism(s) by which PcG act in the chromosome, remain elusive. In particular, no PREs have been identified in mammals yet. The goal of this project is the establishment of a novel model system to study the PcG and trxG function in mammalian cells. In particular, I would like to use the human and mouse neural stem cells (NSCs). NSCs have been shown to have a generalized potential in adopting any cell fate. Thus, beyond their tremendous therapeutic potential, they provide an ideal and intriguing model system to study the role chromosomal components and specialized DNA elements in the regulation of cell identity during differentiation. In addition, the completion of genome sequencing projects has suddendly provided the possibility to evaluate the role of all genes at a global level. In particular, the microarray and biochips technologies allow the simultaneous analysis of thousands of genes. Here, in order to identify all PcG and trxG target genes, I propose a novel approach combining an in vivo chromatin technique for the identification of target sites of chromosomal proteins with biochips.