The central theme of our research is the regulation of gene expression, with the goal of understanding transcriptional regulation in eukaryotes at the molecular level. Problems in gene regulation underlie many human diseases. We study gene regulation in budding yeast because of the powerful genetic and molecular tools that are available. Importantly, the transcription regulatory machinery is conserved between yeast and vertebrates, and insights gained from studies in yeast are generally universal.
The yeast HO gene is transiently expressed during the cell cycle and is expressed in only one of the two cells following mitotic division. Our studies on activation of HO show that chromatin disassembly occurs in waves both along the length of the promoter and during the cell cycle, and three different chromatin factors are required for disassembly of nucleosomes, each at different regions of the HO promoter have shown that which is transiently expressed during the cell cycle in only one of the two cells following mitotic division.
Specific gene expression is controlled by transcription factors binding to elements present in promoters and enhancers. Yeast has two transcription factors, Swi5 and Ace2, that show similar patterns of cell cycle regulation, that have nearly identical zinc finger DNA-binding domains, and recognize the same DNA sequences in vitro. Despite these similarities, Swi5 and Ace2 activate transcription of different genes in vivo, and we are working to understand the mechanisms underlying this promoter specificity.
We are also studying the FACT chromatin reorganizing complex, and its role in regulating transcription initiation and elongation.