The regulation of gene expression plays a pivotal role in all aspects of biology, from the manner in which bacteria respond to their environment to the differentiation of tissues in higher eukaryotes. In the era of genomics, proteomics, and metabolomics, however, biologists are still bereft of a generally applicable method for rapid determination of the regulatory logic underlying the pattern of gene expression in a bacterial cell under a given set of conditions. This logic arises in large part from the binding of transcription factors (TFs) which can either repress or activate expression of nearby genes. We have recently developed a method enabling the simultaneous measurement of the complete regulatory state of bacterial cells under physiological conditions, in the form of a map of protein binding occupancies throughout the genome. This is accomplished by physically separating protein-DNA complexes from bulk genomic DNA, sequencing the footprinted complexes, and then applying a statistical mechanics-based model to identify protein occupancies. The newly developed method is applicable to any bacterium without the need for prior knowledge of its regulatory network, and will allow the rapid dissection of bacterial responses to environmental stresses.View Large Image | View Hi-Res Image | Download PowerPoint Slide