Activation of bacterial transcription by distortion of promoter base pairing

Bacterial RNA polymerase binds and unwinds promoter DNA to initiate transcription. The process is often inefficient and can be stimulated by activator proteins. For example, many activators bind RNA polymerase and promoters simultaneously, stabilizing their interaction. Working with the multiple antibiotic resistance activator (MarA) protein of Escherichia coli, we have discovered an alternative mechanism. We show that, when bound upstream of the flgBCDEFGHIJ/KL operon, MarA perturbs base pairing adjacent to its DNA target. This compensates for inefficient duplex unwinding by RNA polymerase and, as a result, activates transcription. Consistent with our model, an appropriate base pair mismatch mimics the effect of, and removes the need for, MarA. As many regulators alter DNA conformation, we suggest that this mechanism of activation could be commonplace.