Model of Transcriptional Activation by MarA in Escherichia coli

TL;DR

This paper presents a mathematical model of MarA-mediated transcriptional activation in E. coli, revealing activation mechanisms involving kinetic acceleration rather than recruitment, which challenges traditional views.

Contribution

The study introduces a novel kinetic model explaining MarA activation, emphasizing acceleration of transcription steps over polymerase recruitment, supported by experimental data.

Findings

MarA accelerates post-binding transcription steps

RNA polymerase binds promoters with high occupancy without MarA

Activation may involve polymerase repulsion and kinetic acceleration

Abstract

We have developed a mathematical model of transcriptional activation by MarA in Escherichia coli, and used the model to analyze measurements of MarA-dependent activity of the marRAB, sodA, and micF promoters in mar-rob- cells. The model rationalizes an unexpected poor correlation between the mid-point of in vivo promoter activity profiles and in vitro equilibrium constants for MarA binding to promoter sequences. Analysis of the promoter activity data using the model yielded the following predictions regarding activation mechanisms: (1) MarA activation of the marRAB, sodA, and micF promoters involves a net acceleration of the kinetics of transitions after RNA polymerase binding, up to and including promoter escape and message elongation; (2) RNA polymerase binds to these promoters with nearly unit occupancy in the absence of MarA, making recruitment of polymerase an insignificant factor in activation of these promoters; and (3) instead of recruitment, activation of the micF promoter might involve a repulsion of polymerase combined with a large acceleration of the kinetics of polymerase activity. These predictions are consistent with published chromatin immunoprecipitation assays of interactions between polymerase and the E. coli chromosome. A lack of recruitment in transcriptional activation represents an exception to the textbook description of activation of bacterial sigma-70 promoters. However, use of accelerated polymerase kinetics instead of recruitment might confer a competitive advantage to E. coli by decreasing latency in gene regulation.