A large number of genes required for Drosophila development function by regulating the transcription of other genes. I am interested in the connection between the basic transcription machinery and pattern formation. My work shows that specific mutations in RNA polymerase II (polII) itself can disrupt different discrete steps in developmental processes. Many of the developmental defects caused by polII alleles mimic those elicited by loci assumed to encode transcription factors. This observation suggests that polII plays an active role in choosing which genes to transcribe, possibly by interacting either directly or indirectly with developmentally regulated DNA binding proteins. To fully understand development it is essential to define the interactions between regulatory proteins and polII. In order to accomplish this goal I have begun to identify mutations that interact with existing mutant alleles of polII. I have isolated mutations in other genes (extragenic) that either enhance or suppress mutant phenotypes elicited by certain polII alleles. These might encode proteins that interact functionally with polII and will include: 1) previously undescribed subunits, 2) proteins required for modification of polymerase, 3) proteins that regulate gene expression during development, and 4) proteins that maintain chromatin structure or nuclear architecture. The primary goal of this research is to elucidate the mechanism by which transcriptional regulation controls development. This will be accomplished by the determination of the protein products encoded by genes identified as enhancer and suppressor mutations and the defining of the molecular basis of the interactions between these and known subunit mutations.
