This application requests support for the Fifth Gordon Research Conference on Epigenetic Regulation of Gene Expression to be held at Holderness School, New Hampshire, August 10-15, 2003. Epigenetic regulation is mediated by the creation and maintenance of heritable, but potentially reversible, changes in chromatin structure and/or DNA methylation, which alters gene expression without altering DNA sequence. Epigenetic effects have been discovered in many organisms and they comprise some of the most intriguing and actively investigated phenomena with relevance to both basic and applied science. For example, loss of epigenetically imprinted events on the chromosome contribute to tumor progression in many human cancer types. In addition, mutations in genes encoding DNA methyltransferase and a methyl-DNA binding protein lead to mental retardation in the form of immunodeficiency, centromeric instability, and facial anomalies (ICF syndrome) and Rett syndrome, respectively, while loss of imprinting leads to childhood diseases such as Angelman and Prader-Willi syndromes. There is increasing evidence that epigenetic silencing contributes to variation among clones, which has profound implications for stem cell research in the biomedical arena, as well as for the cloning of farm animals in agriculture. Remarkably, the molecular mechanisms that underlie epigenetic silencing are conserved in fungi and in plants, where they impact transgene silencing and somaclonal variation, as well as contributing significantly to natural variation and a host of classical genetic anomalies, such as paramutation. There has been tremendous progress in elucidating these mechanisms in the last few years and this will be a major focus of this conference. Invited speakers are leading researchers working on fungal, plant, and animal models as well as human disease, who will cover topics such as control and function of DNA methylation, histone modifications, RNA interference, imprinting, X-inactivation, prions, epigenetics and disease, genome defense systems, paramutation, and position effects. The Epigenetics Gordon Conference provides a unique opportunity for researchers working on related phenomena in different organisms to come together and exchange recent results and ideas. It is in a cross-disciplinary environment such as this that intellectual leaps occur and innovative ideas flourish.
