The properties of a cell are determined by the information encoded in its genome. Understanding how such information is differentially and dynamically retrieved in response to environmental changes and cellular needs is a major challenge facing molecular biology. The focal point of our research is a multisubunit RNA polymerase, the enzyme that carries out the first step in gene expression, synthesis of RNA. We study several classes of RNA polymerases with the aim of understanding the fundamental aspects of transcription regulation, catalytic mechanism, and developing medically relevant transcription inhibitors.