Long & Medium-Term Research: Investigation of the Mechanism of Nucleosome Removal from the PHO5 Promoter This award is under the Long and Medium-Term Research at Foreign Centers of Excellence Program, which enables U.S. scientists and engineers to conduct three to twelve months of research abroad at research centers of proven excellence. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twelve-month postdoctoral research visit by Dr. John P. Svaren to go to the University of Munich to work with Dr. Wolfram Horz. Their project is designed to explore the ability of eukaryotic trans-activators to modulate chromatin structure. Numerous in vitro studies have shown that nucleosomes can block binding of critical transcription factors to a DNA template. In addition, the promoters of most actively transcribing genes appear to be at least partially nucleosome-free. Therefore, since virtually all eukaryotic DNA is normally packaged into nucleosomes, there must be some mechanism to keep nucleosomes from occupying critical promoter elements of active genes. Study of the PHO5 gene in the yeast Saccharomyces cerevisiae should give more insight into this process. Upon induction of PHO5 transcription (by phosphate starvation), four nucleosomes are removed from the promoter region. Several experiments by Dr. Wolfram Horz's lab suggest that the trans-activator, PHO4, is responsible for triggering the nucleosome loss. Drs. Svaren and Horz's project is designed to map the protein domain of PHO4 that is involved in nucleosome dissolution. In particular, the acidic domain of PHO4 will be investigated to see whether it is necessary or sufficient for this transformation. These experiments could potentially reveal another mechanism whereby trans-acting factors regulate transcription. The award recommendation provides funds to cover international travel, a stipend for twelve months and a dependents' allowance.
