Transcriptional regulation of fis operon involves a module of multiple coupled promoters

The transcription of the Escherichia coli fis gene is strongly activated during the outgrowth of cells from stationary phase. The high activity of the promoter of the fis operon requires the transcription factor IHF. Previously, we identified a divergent promoter, div, located upstream of the fis promoter. In this study we demonstrate that at least two additional promoters, designated fis P2 and fis P3, are located in the control region of the fis operon. The fis P2 and div promoters overlap completely, whereas fis P3 and div P are arranged as face-to-face divergent promoters. We show that the div and the tandem fis promoters counterbalance each other, such that their activity is kept on a lower than potentially attainable level. Furthermore, we demonstrate an unusual activation mechanism by IHF, involving a coordinated shift in the balance of promoter activities. We infer that these coupled promoters represent a regulatory module and propose a novel "dynamic balance" mechanism involved in the transcriptional control of the fis operon.