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 s tructure in transcriptional regulation(1). Here we describe how the tr anscription factor MerR can mediate repression as well as activation t hrough stereospecific modulation of DNA structure. The repressor form of MerR binds between the -10 and -35 promoter elements of the bacteri al mercury-detoxification genes, P-T, allowing RNA polymerase to form an inactive complex with P-T and MerR at this stress-inducible promote r(2,3). Upon mercuric ion binding, Hg-MerR converts this polymerase co mplex into the transcriptionally active or 'open' form(2-4). We show h ere that MerR bends DNA towards itself in a manner similar to the bact erial catabolite-activator protein CAP, namely at two loci demarked by DNase I sensitivity, and that the activator conformation, Hg-MerR, re laxes these bends. This activator-induced unbending, when coupled with the previously described untwisting of the operator(5), remodels the promoter and makes it a better template for the poised polymerase.