This project is part of an ongoing investigation of Suppressor of sable [Su(s)], a nuclear protein that regulates gene expression in the model organism Drosophila by an unknown mechanism. Su(s) inhibits the expression of certain mutant alleles of genes that produce aberrant RNAs. The activity of Su(s) is also required for normal expression of certain developmentally-regulated genes. Recent studies have shown that Su(s) is rapidly recruited to a subset of the heat shock loci during heat shock, and these experiments will investigate the role Su(s) plays in the heat shock response. Genomic microarray analysis will be used to determine the global effect of su(s) mutations on the heat shock response and to determine if the expression of genes at heat shock loci is altered in su(s) mutants. Nuclear run-on experiments will be used to evaluate the effect of su(s) mutations on transcription of heat-shock inducible genes. Chromatin immunoprecipitation experiments will map, at a high level of resolution, the site of Su(s) localization within the 87C region which contains three heat-shock inducible hsp70 genes and multiple alpha/beta repeat elements. This study will establish whether Su(s) acts at the level of transcription and define specific molecular processes that depend on the activity of this protein. The intellectual merit of this work lies in its potential to provide novel insights into the complex mechanisms that integrate various processes in nuclear pre-mRNA metabolism in higher organisms. The broader impact lies in its contribution to the development of human resources in science. This project has supported the research training of numerous graduate and undergraduate students. Furthermore, the PI is actively involved in developing programs to enhance the academic experience of undergraduate science majors and to increase the participation of underrepresented minority groups in scientific research.
