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

Abstract

Negative DNA superhelicity can destabilize the local B-form DNA structure and can drive transitions to other conformations at susceptible sites, In-a-molecule containing multiple susceptible sites, superhelicity can couple these alternatives together, causing them to compete. In principle, these superhelically driven local structural transitions can be either facilitated or inhibited by proteins that bind at or near potential transition sites. If a DNA region that is susceptible to forming a superhelically induced alternate structure is stabilized in the B-form by a DNA-binding protein, its propensity for transition will be transferred to other sites within the same domain. If one of these secondary sites is in a promoter region, this transfer could facilitate open complex formation and thereby activate gene expression. We previously proposed that a supercoiling- dependent, DNA structural transmission mechanism of this type is responsible for the integration host factor-mediated activation of transcription from the ilvP(G) promoter of Escherichia coli (Sheridan, S. D., Benham, C. J. and Hat. field, 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 integration host factor-mediated transcriptional activation, and thereby delay its occurrence.