We are interested in understanding the regulation of eukaryotic gene expression at the level of transcription and chromatin structure. Our studies are done in the budding yeast S. cerevisiae and in the distantly related fission yeast S. pombe. Both of these yeasts share most fundamental aspects of gene regulation with larger eukaryotes, including Drosophila and humans. As unicellular eukaryotes, yeast cells are particularly valuable for understanding transcriptional responses to many types of changes, including changes in oxygen, carbon, and nitrogen limitations, and changes during mating and meiosis. We use several related experimental approaches in our studies, including genetics, functional genomics. and biochemistry.
One broad area of focus in our lab is the study of a transcriptional coactivator complexes that regulate transcription. One of these complexes, named SAGA, is a complex of 19 proteins that controls the expression of a large number of genes in vivo. SAGA can control transcription by distinct mechanisms, including histone acetylation. We are interested in several aspects of SAGA, including its mechanisms of action in response to environmental changes, and its assembly and structure. Two other classes of coactivator complexes we study are nucleosome remodeling complexes, which modify nucleosome structure to allow other factors bind to their sites, and Mediator, which controls the distance over which transcriptional activation can occur.
Another area of study addresses the regulation of histone levels. Our work has shown that histone levels are controlled both by regulating transcription of histone genes, by a factor called Spt10, and by controlling the actual number of histone genes by a specific gene amplification mechanism. Another factor we study, Spt6, controls the density of nucleosomes across chromosomes.
In addition to these studies, our lab has interests in many other aspects of transcriptional control. These include the transcriptional responses to changes in oxygen, nitrogen, and carbon levels, and the control of meiosis. Studying these conserved processes in yeast will allow us to understand their functions both in vivo and in vitro.
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References:
- Martens, J.A., Wu, P.-Y.J., and Winston, F. 2005. Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae. Genes & Dev. 19, 2695-2704.
- Nourani, A., Robert, F., and Winston, F. 2006. Evidence that Spt2/Sin1, and HMG-like factor, plays roles in transcription elongation, chromatin structure, and genome stability in S. cerevisiae. Mol. Cell. Biol. 26, 1496-1509.
- Libuda, D.E., and Winston, F. 2006. Amplification of histone genes by circular chromosome formation in Saccharomyces cerevisiae. Nature 443, 1003-1007.
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