The long-term goal of this laboratory is to formulate an understanding of the molecular mechanisms operating to regulate expression of class II genes. This will be accomplished through the characterization of the proteins involved, and their various protein-DNA and protein-protein interactions. To this end, the overall aim of this proposal is to continue and expand studies now in progress on a novel heterodimeric factor, Dr1/DRAP1, that interacts with a key component of the RNA polymerase II transcription machinery. This interaction results in repression of class II gene expression. Regulation of gene expression is a complex process that can be achieved at multiple steps. Studies have demonstrated that initiation of transcription is a primary site for regulation. The first step during formation of a transcription competent complex is the binding of TFIID to the TATA motif, providing a recognition site for the association of RNA polymerase II and auxiliary proteins. TFIID also interacts with activator proteins. A great deal of effort has been directed towards the isolation of proteins that activate transcription. However, an equally important mechanism for regulating gene expression is repression. Studies carried out during the past years have uncovered a mechanism for repression involving protein:protein interactions.
