Diverse mechanisms of transcriptional activation in the Escherichia coli marA/soxS/rob regulon

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The MarA, SoxS and Rob transcription factors activate the same ~40 genes (the marA/soxS/rob regulon) of the E. coli chromosome resulting in different levels of resistance to a wide array of antibiotics and to superoxides. We previously examined the relationship between activator concentration and the activity of 10 promoters of the regulon (Martin et al., J. Mol. Biol. 380 (2008) 278). We found that the MarA concentrations needed for half-maximal stimulation varied substantially among the promoters, and that only the marRAB, micF, and sodA promoters were saturated at the highest level of MarA obtained. Surprisingly, we found that the correlation between the MarA concentration needed for half-maximal promoter activity in vivo and marbox binding affinity in vitro was poor. We have developed a mathematical model of marRAB, micF, and sodA promoter activity in which MarA modulates both the affinity of RNA polymerase (RNAP) for the promoter and the kinetics of transcription initiation. The model rationalizes the poor correlation between promoter activity and MarA binding affinity, and makes some surprising predictions about how these promoters are activated by MarA. For example, it predicts that factors other than recruitment are necessary to explain activation of marRAB, micF, and sodA; the same might hold for activation of other σ70 promoters in E. coli and other prokaryotes.

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