DNA-bend modulation in a repressor-to-activator switching mechanism

RECENT discoveries of activator proteins that distort DNA but bear no obvious activation domains have focused attention on the role of DNA structure in transcriptional regulation¹. Here we describe how the transcription factor MerR can mediate repression as well as activation through stereospecific modulation of DNA structure. The represser form of MerR binds between the −10 and −35 promoter elements of the bacterial mercury-detoxification genes, P_T, allowing RNA polymerase to form an inactive complex with P_T and MerR at this stress-inducible promoter^{2, 3}. Upon mercuric ion binding, Hg−MerR converts this polymerase complex into the transcriptionally active or 'open' form²⁻⁴. We show here that MerR bends DNA towards itself in a manner similar to the bacterial catabolite-activator protein CAP, namely at two loci demarked by DNase I sensitivity, and that the activator conformation, Hg−MerR, relaxes these bends. This activator-induced unbending, when coupled with the previously described untwisting of the operator5, remodels the promoter and makes it a better template for the poised polymerase.