About Student Research
Eric Ross (1996–2001)
Importance of DNA flexibility in promoter architecture
After graduating from Yale University, Eric Ross came to the laboratory for Ph.D. work to explore fundamental features of transcription activation mechanisms in mammalian cells. Eric studied the hypothesis that the length and structure of DNA intervening between a transcription factor binding site and the basal promoter (TATA box) could influence gene activation. It was considered possible that activation occurs by DNA looping, and that some loop geometries might be favorable. Eric created a large number of templates altering activator spacing and the presence of intrinsically-curved elements. He used in vitro transcription in HeLa cell nuclear extract with addition of recombinant transcription activation proteins to explore these problems. Eric's work revealed independence of in vitro gene activation from details of the spacer DNA, pointing to linear distance as the main factor in activator strength. This surprising result led to a rediscovery of the profound ability of heat-resistant factors in mammalian nuclei to enhance the apparent flexibility of DNA. The implicated high mobility group B (HMGB) proteins are sequence nonspecific, but abundant and powerful in their ability to change DNA physical properties. Eric also contributed important theoretical work to improved in vitro assays of DNA curvature.