BBS Faculty Member - Fred Wiston

Fred Winston

Department of Genetics

Harvard Medical School
New Research Building, Room 239
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-7768
Fax: 617-432-6506
Email: winston@genetics.med.harvard.edu
Lab Members: 4 postdoctoral fellows, 2 graduates students
Visit my lab page here.



Our lab studies eukaryotic transcription and chromatin structure, using both the budding yeast, S. cerevisiae, and the distantly related fission yeast, S. pombe. These yeasts share fundamental aspects of gene regulation with mammals, including many of the factors required for transcription such as RNA polymerase II, general transcription factors, transcriptional coactivators, and factors that control and modify chromatin structure. However, these two yeasts are also quite distinct in interesting and informative ways, such as in their mechanisms of heterochromatin formation and transcriptional silencing.

Both
S. cerevisiae and S. pombe are particularly valuable model organisms for several reasons. First, powerful genetic approaches can be used. Any desired change can be made in either genome and its consequences analyzed. In addition, high-resolution genetic screens and selections can be performed to study any aspect of gene regulation. Second, the small genomes of these yeasts facilitate many types of genome-wide approaches, including those to measure mRNA levels, nucleosome positions, and the binding of transcription factors. The small genome size also allows the study and elucidation of complex traits. Third, as unicellular eukaryotes, yeast cells are valuable for biochemical analysis of protein complexes and post-translational modifications. In our lab, we use all of these types of approaches to understand several different aspects of transcriptional control and chromatin structure.

Studies in our lab are in several areas. One centers around a transcriptional coactivator named SAGA, a complex of 19 proteins that controls the expression of many genes
in vivo, particularly those that respond to environmental stresses. A second area focuses on factors that control the ability to overcome the repressive effects of nucleosomes on transcription. These factors include histones, the protein components of nucleosomes, Swi/Snf, a nucleosome remodeling complex, and Spt6, a large, highly acidic protein that is required for controlling the integrity of transcription across the genome. Our studies have shown that in S. cerevisiae spt6 mutants, transcription is able to initiate from hundreds of cryptic promoters throughout the genome that are normally silent. Our studies of S. pombe spt6 mutants have shown that they are defective in heterochromatin formation and transcriptional silencing. Other studies in our lab address how yeast cells control the distance over which transcriptional activation can occur, and the regulation of transcription in response to changes in glucose and oxygen levels.



Last Update: 6/12/2014



Publications

For a complete listing of publications click here.

 


 



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