Eukaryotic gene regulation
The basic molecular mechanisms of transcriptional regulation are highly conserved throughout the eukaryotic kingdom. Transcriptional regulation in response to environmental and developmental cues is mediated primarily by the combinatorial and synergistic action of specific DNA binding proteins on components of the general transcription machinery. This laboratory combines genetic, molecular, and biochemical approaches available in yeast to investigate a variety of issues among which are the following: 1) functional analysis of the TATA binding protein, the universal transcription factor that is required for initiation by all 3 RNA polymerases, and its associated factors (TAFs); 2) mechanisms of transcriptional activation and synergy; 3) the relationship between the structure of DNA in the nucleus (chromatin) and gene expression, 4) global transcriptional repression mechanisms; 5) protein protein interactions between activators, repressors, and the basic transcription machinery; 6) the role of the Ras pathway in mediating transcriptional events in response to rapid environmental signals. In addition, the mechanism of oncogenic transformation by AP 1 transcription factors (Jun and Fos) is being studied, with particular emphasis on the identification and characterization of oncogenically relevant target genes.