Local DNA topology and gene expression: the case of the leu-500 promoter.

Many promoters are sensitive to DNA supercoiling, and it is becoming apparent that this may play an important role in gene regulation. The twin supercoiled-domain hypothesis (Liu and Wang, 1987) proposes that transcription can lead to local variation in supercoiling. The mutant leu-500 promoter has presented a long-standing problem to the understanding of the control of promoter function by DNA supercoiling. This promoter is activated by mutations in the gene encoding topoisomerase I, but is apparently unaffected by mutations in the genes encoding DNA gyrase. We propose a model to explain the anomalous regulation of this promoter, based on the twin supercoiled-domain model. This allows us to account for the unusual properties of the leu-500 promoter, and confirms the biological importance of the twin supercoiled-domain model. We suggest that such topological coupling between promoters may be general, leading to co-operativity and anti-co-operativity between divergent promoter pairs.