Activation and repression of transcription initiation by a distant DNA structural transition.

Negative superhelical tension can drive local transitions to alternative DNA structures. Long regions of DNA may contain several sites that are susceptible to forming alternative structures. Their relative propensities to undergo transition are ordered according to the energies required for their formation. These energies have two components - the energy needed to drive the transition and the energy relieved by the partial relaxation of superhelicity that the transition provides. This coupling can cause a complex competition among the possible transitions, in which the formation of one energetically favourable alternative structure may inhibit the formation of another within the same domain. In principle, DNA structural competitions can affect the structural and energetic requirements for the initiation of transcription at distant promoter sites. We have tested this possibility by examining the effects of structural transitions on transcription initiation from promoter sites in the same superhelical domain. Specifically, we describe the effects of the presence of a Z-DNA-forming DNA sequence on the basal levels of expression of two supercoiling-sensitive promoters of Escherichia coli, ilvPG and gyrA. We demonstrate transcriptional repression of the ilvPG promoter and activation of the gyrA promoter. We present evidence that this regulation is effected by the superhelically induced B- to Z-DNA transition in a manner that is both orientation and distance independent. We discuss the mechanism of topological coupling between left-handed Z-DNA and the regulation of promoter activity. We also discuss the possibility that the coupling of DNA structural transitions and transcriptional activity might be used as a general regulatory mechanism for gene expression.