A promoter relay mechanism for sequential gene activation

The effect of DNA supercoiling on gene expression is dependent not only on specific genes but also on the sequence context of the genes. This position-dependent supercoiling effect on gene activation is best illustrated in the study of the suppression of the leu-500 mutation of the leuABCD operon in a Salmonella typhimurium topA mutant. In this communication, we report a novel promoter relay mechanism whereby several genes are sequentially expressed in a position-dependent manner: the ilvIH promoter (pilvIH) activates a cryptic leu0 promoter (pleu0) located between the two divergently arrayed ilvIH and leu-500 promoters. Both the cis-acting pleu0 activity and the trans-acting Leu0 protein are necessary for subsequent activation of the leu-500 promoter (pleu-500). Furthermore, pleu0 can be functionally replaced with the inducible tac promoter (ptac) for leu-500 activation, suggesting that transcription-driven DNA supercoiling underlies the relay mechanism. This is the first example of several related genes communicating via a promoter relay mechanism for their coordinated expression.