Objective Epigenetics refers to heritable changes in gene expression patterns, brought about by modifications to DNA and chromatin. Aberrant epigenetic activity was shown to play important roles in the tumorigenic process. Two major epigenetic systems are known: DNA methylation and the histone modification machinery, an important component of which is the Polycomb Repressive Complexes (PRC) system. Recent works have suggested that a link between the two systems exists in cancer cells. Previous work on the interaction between DNA methylation and PRC activity was mostly limited to studies of a small number of genes leading to partial and conflicting results. I propose a long term comprehensive study that aims to examine the correlated epigenetic changes in these systems occurring through the spectrum of the tumorigenic process. This is made possible by a new methodology we have developed involving simultaneous genome-wide profiling of DNA methylation and PRC activity followed by robust computational analysis of the data. This gives us a unique ability to probe correlated changes of the various epigenetic systems. The project will be based on an established lab-computational-biotech collaboration and will entail simultaneous genome-wide profiling of epigenetic systems in normal and cancer cells and in various stages of the immortalization/transformation process. Results of the initial phase of this study show significant interplay between the two epigenetic systems. In particular, it appears that the two silencing mechanisms act in parallel to reprogram the cancer epigenome, and that DNA hypermethylation may replace Polycomb based repression near key regulatory genes, possibly reducing their regulatory flexibility. I expect the project to lead to a characterization of the gradual evolution of epigenetic states during the tumorigenic process, and their contribution to the transformation of normal cells to cancer cells. Fields of science natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsepigenetics Keywords Cancer DNA methylation Epigenetics Health sciences Polycomb system Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Call for proposal FP7-PEOPLE-2007-4-3-IRG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT AND HEALTH SERVICES FUND BY THE SHEBA MEDICAL CENTER EU contribution € 100 000,00 Address TEL HASHOMER SHEBA MEDICAL CENTER 52621 Ramat Gan Israel See on map Activity type Research Organisations Administrative Contact Moshe Barak (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
