DNA supercoiling and transcription control: a model from the study of suppression of the leu-500 mutation in Salmonella typhimurium topA- strains.

DNA supercoiling is known to modulate gene expression. The functional relationship between DNA supercoiling and transcription initiation has been established genetically and biochemically. The molecular mechanism whereby DNA supercoiling regulates gene expression remains unclear however. Quite commonly, the same gene responds to the same DNA supercoiling change differently when the gene is positioned at different locations. Such strong positional effects on gene expression suggest that rather than the overall DNA supercoiling change, the variation of DNA supercoiling at a local site might be important for transcription control. We have started to understand the local DNA supercoiling dynamic on the chromosome. As a primary source of local DNA supercoiling fluctuation, transcription-driven DNA supercoiling is important in determining the chromosome supercoiling dynamic and theoretically, therefore, for transcription control as well. Indeed, by studying the coordinated expression of genes in the ilvIH-leuO-leuABCD gene cluster, we found that transcription-driven DNA supercoiling governs the expression of a group of functionally related genes in a sequential manner. Based on the findings in this model system, we put forward the possible mechanisms whereby DNA supercoiling plays its role in transcription control.