Summary
(PcG) and trithorax group (trxG) proteins act at the cross-roads of chromatin regulation, stem cell biology, development and disease and they have become one of the focal points of current biological research. The main goal of this proposal is to understand the biochemistry and regulatory networks controlled by the PcG/trxG system in stem cell biology. Recent research has emphasized the importance of epigenetic gene control for stem cell self-renewal and differentiation. Results from us and others suggest that selective PcG and trxG proteins appear to be differentially expressed in stem cells, pluripotent cells and fully differentiated cells. Our initial analysis suggests that whereas many PcG/trxG proteins are ubiquitously expressed, selective subunits display a highly differential pattern of expression. There is accumulating evidence that they play an important role in stem cell maintenance and the switch from pluripotent to differentiated cells. The major objectives of our research will be: (1) characterization of the role of SWI/SNF class remodelers in stem cell biology and (2) determination of the function of chromatin ubiquitylation and deubiquitylation in stem cell gene expression programs. We will use a fully integrated state-of-the-art proteomics and systems biology approach. We will map the protein-protein interaction and signaling networks that regulate chromatin status and their effects on gene expression during stem cell self-renewal and differentiation.