We are interested in the control of transcription of eukaryotic genes, and in particular the basic molecular mechanisms governing the interaction of transcription regulatory factors with each other and with specific DNA sequences. Specific projects include: (1) analysis of 5S rRNA gene transcription by RNA polymerase III, (2) understanding specific DNA (and RNA) sequence recognition by zinc finger proteins, particularly the archetypal zinc finger protein TFIIIA, (3) applying novel approaches to the study of the mechanism of transcriptional activation, and (4) defining the mechanism of transcription termination using a unique kinetic approach. The model systems we study include the frog Xenopus laevis and the yeasts Saccharomyces cerevisiae (budding yeast) and Schizosaccharomyes pombe (fission yeast). We also make use of cultured eukaryotic cell lines.

Our experimental approaches include rigorous, quantitative analyses of in vitro transcription reactions and of the interactions of transcription factors with each other and with their DNA targets. This in vitro biochemical approach is complemented by genetic analyses in yeast and, at times, by experiments making use of microinjection into and manipulation of Xenopus eggs and embryos. Our efforts are focused on understanding the fundamental molecular mechanisms governing gene expression, but have sometimes been known to have practical consequences. For example, our recent studies of certain mutant forms of TFIIIA are relevant to the engineering of novel proteins that make use of the zinc finger motif to recognize specific DNA sequences in gene therapy or gene targeting approaches.