Regulating levels of gene expression is central to all of biology. A primary point for controlling gene expression is during mRNA transcription, which occurs as the enzyme RNA polymerase II (Pol II) synthesizes an RNA copy of the DNA in protein encoding genes. The ultimate goal of my research is to arrive at a detailed understanding of the Pol II transcription reaction and how it is regulated. We use several different approaches and systems to achieve this goal. For example, we are studying how the cellular Pol II transcription program globally changes in response to stress. In addition, we are using single molecule assays to understand the mechanisms, kinetics, and physical parameters that govern transcription factor complexes. We are also interested in how specific transcriptional activator proteins and architectural proteins bind to DNA and nucleosomes to contribute to regulating transcription. In addition to understanding Pol II transcription, we are interested in post-transcriptional mechanisms to control gene expression; in particular downregulation of gene expression by microRNAs (miRNAs). Essential to understanding the mechanisms by which any miRNA controls a cellular process is knowing the full set of target mRNAs that it downregulates, which of these targets strongly impact cellular phenotype, and how miRNAs themselves are post-transcriptionally regulated. Addressing these issues are primary goals of our work, using differentiation of skeletal muscle cells as a model system.
keywords
mechanisms of mammalian RNA polymerase II transcription, non-coding RNA regulators of gene expression, single molecule studies of transcription complexes
