 Laura RuscheAssistant Professor of BiochemistryChromatin-mediated gene repressionResearch ProgramWelcome to the Rusche Lab! We study the molecular mechanisms of chromatin-mediated gene repression in budding yeast. In particular, we are interested in how repressive chromatin forms and spreads (or not) along chromosomes. In Saccharomyces cerevisiae, long-range silencing at the mating-type loci is mediated by the Sir proteins. Sir2p is a histone deacetylase, and Sir3p and Sir4p bind to histone tails. Together, these three proteins spread along the chromosome, forming a repressive chromatin structure. By way of contrast, we are studying a second repressive complex, the Sum1 complex, which does not spread. Like the Sir complex, the Sum1 complex includes a deacetylase, in this case Hst1p, which is highly related to Sir2p. In addition, Sum1p interacts with histone tails. However, despite these similarities to the Sir complex, the Sum1 complex acts locally at promoters and does not spread. Interestingly, a single amino acid change in Sum1p causes the complex to behave like the Sir complex and to spread, creating a new species of silenced chromatin. This SUM1-1 mutation presents a unique opportunity to discover how the spreading process is regulated. Finally, we are exploring the evolution of gene silencing in fungi. The deacetylases Sir2p and Hst1p, which act in the Sir and Sum1 complexes respectively, are paralogs that arose in a whole-genome duplication that occurred in the ancestry of S. cerevisiae. We are investigating the function of the ancestral Sir2/Hst1p by studying fungal species that diverged from S. cerevisiae prior to the duplication event. |
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