Living cells have developed sophisticated mechanisms to control which parts of their genomes are being expressed at any given time. We are studying two global gene responses of bacteria, using Bacillus subtilis as a highly tractable model system. The first is a response to stress in which bacteria sense hazardous environmental changes and induce the expression of genes whose products can lessen the effects of the hazard. The second is a controlled program of gene expression that, once triggered, allows the bacterium to undergo a simple differentiation (sporulation). Both of these responses are controlled by a reprogramming of the cell's "gene reading" enzyme, RNA polymerase; however, the mechanism for each of the reprogrammings is unique. How does a single cell "know" that it is in a stressful environment? What is the biochemical process that it uses to convey the stress's presence to its transcription machinery? How does a cell orchestrate the pattern of gene expression during differentiation to insure that the correct genes are turned on at the right times for its developing structures to form properly? Using a combination of genetic and biochemical techniques, we are learning the answers to these questions, identifying the factors involved and the mechanisms by which these factors communicate their messages to the proper targets.