Inhibition of DNA supercoiling-dependent transcriptional activation by a distant B-DNA to Z-DNA transition

Negative DNA superhelicity can destabilize the local B-form DNA structure a nd can drive transitions to other conformations at susceptible sites. In a molecule containing multiple susceptible sites, superhelicity can couple th ese alternatives together, causing them to compete. In principle, these sup erhelically driven local structural transitions can be either facilitated o r inhibited by proteins that bind at or near potential transition sites, If a DNA region that is susceptible to forming a superhelically induced alter nate structure is stabilized in the B-form by a DNA-binding protein, its pr opensity for transition will be transferred to other sites within the same domain, If one of these secondary sites is in a promoter region, this trans fer could facilitate open complex formation and thereby activate gene expre ssion. We previously proposed that a supercoiling-dependent, DNA structural transmission mechanism of this type is responsible for the integration hos t factor-mediated activation of transcription from the ilvP(G) promoter of Escherichia coli (Sheridan, S, D,, Benham, C. J, & Hatfield, G, W, (1998) J , Biol, Chem, 273, 21298-21308), In this report we confirm the validity of this mechanism by demonstrating the ability of a distant Z-DNA-forming site to compete with the superhelical destabilization that is required for inte gration host factor-mediated transcriptional activation, and thereby delay its occurrence.