The Workman lab uses yeast, fruit flies and mammalian cells to study multiple factors that activate and repress transcription. Thus far, they have characterized players in the repressive Set2 pathway primarily in yeast, in part because yeast represents an ideal organism for mutational analysis and has a fairly small genome6,000 genes compared to the 25,000 or so in humans or mice.
Smolle notes that although yeast genomes are simpler, the principles that govern Set2 activity in yeast will likely hold true for its human counterparts, among them the human protein SETD2. "Yeast has a single methylase, while humans have several, and flies and humans have several Isw1-like proteins," she says. "While you cannot equate one with the other precisely, you can be reasonably sure that what happens in yeast happens in humans as well but tends to be more complicated."
Workman agrees, adding that these discoveries have significant implications for human disease. "Strikingly, the human homolog of Set2, SETD2, is implicated as a tumor suppressor in breast cancer and in renal carcinoma, and those cells are deficient in the SETD2 methylation mark," he says. "These findings strongly suggest that SETD2 could be important in controlling cell growth and preventing tumors. Thanks to yeast, we now know more about how Set2 does that."
|Contact: Gina Kirchweger|
Stowers Institute for Medical Research