Escherichia coliLrp regulates one-third of the genome via direct, cooperative, and indirect routes

The global regulator Lrp plays a crucial role in regulating metabolism, virulence and motility in response to environmental conditions. Lrp has previously been shown to activate or repress approximately 10% of genes in Escherichia coli . However, the full spectrum of targets, and how Lrp acts to regulate them, has stymied earlier study. We have combined matched ChIP-seq and RNA sequencing under nine physiological conditions to map the binding and regulatory activity of Lrp as it directs responses to nutrient abundance. In addition to identifying hundreds of novel Lrp targets, we observe two new global trends: first, that Lrp will often bind to promoters in a poised position under conditions when it has no regulatory activity, and second, that nutrient levels induce a global shift in the equilibrium between non-specific and sequence-specific DNA binding. The overall regulatory behavior of Lrp, which as we now show regulates 35% of E. coli genes directly or indirectly under at least one condition, thus arises from the interaction between changes in Lrp binding specificity and cooperative action with other regulators.