Competitive behavior of multiple, discrete B-Z transitions in supercoiled DNA

Conformational transitions in topologically constrained duplex DNA necessarily affect and are affected by other transitional processes throughout the entire molecule. This conformational interdependence of discrete sequences within a given superhelical domain arises through a requisite competition for the free energy of supercoiling. Here we present a generalized statistical mechanical analysis of multiple, competing conformational equilibria in superhelical DNA. This model has been applied, using experimentally determined parameters, to the energetic coupling of two independent B-Z transitions. Specifically, we have monitored the extent of B-Z transition, as a function of negative superhelicity, in topoisomers of a plasmid containing two identical d(C-G)n inserts using two-dimensional gel electrophoresis. The theoretical results were found to be in good agreement with the experimental data, and we have used this model to predict the competitive behavior of B-Z transitions within sequences differing in length and sequence composition. This competition is shown to have a profound effect upon the B-Z equilibria of those sequences analyzed, resulting in a complex modulation in the extent of Z-DNA formation as a function of negative superhelicity. These theoretical and experimental results show that DNA sequences separated by large distances are capable of communicating structural information.