 Model of Transcriptional Activation by MarA in Escherichia coliMichael E Wall, David A Markowitz, Judah L Rosner and Robert G Martin PLOS Computational Biology, 2009, vol. 5, issue 12, 1-11 Abstract: The AraC family transcription factor MarA activates ∼40 genes (the marA/soxS/rob regulon) of the Escherichia coli chromosome resulting in different levels of resistance to a wide array of antibiotics and to superoxides. Activation of marA/soxS/rob regulon promoters occurs in a well-defined order with respect to the level of MarA; however, the order of activation does not parallel the strength of MarA binding to promoter sequences. To understand this lack of correspondence, we developed a computational model of transcriptional activation in which a transcription factor either increases or decreases RNA polymerase binding, and either accelerates or retards post-binding events associated with transcription initiation. We used the model to analyze data characterizing MarA regulation of promoter activity. The model clearly explains the lack of correspondence between the order of activation and the MarA-DNA affinity and indicates that the order of activation can only be predicted using information about the strength of the full MarA-polymerase-DNA interaction. The analysis further suggests that MarA can activate without increasing polymerase binding and that activation can even involve a decrease in polymerase binding, which is opposite to the textbook model of activation by recruitment. These findings are consistent with published chromatin immunoprecipitation assays of interactions between polymerase and the E. coli chromosome. We find that activation involving decreased polymerase binding yields lower latency in gene regulation and therefore might confer a competitive advantage to cells. Our model yields insights into requirements for predicting the order of activation of a regulon and enables us to suggest that activation might involve a decrease in polymerase binding which we expect to be an important theme of gene regulation in E. coli and beyond.Author Summary: When environmental conditions change, cell survival can depend on sudden production of proteins that are normally in low demand. Protein production is controlled by transcription factors which bind to DNA near genes and either increase or decrease RNA production. Many puzzles remain concerning the ways transcription factors do this. Recently we collected data relating the intracellular level of a single transcription factor, MarA, to the increase in expression of several genes related to antibiotic and superoxide resistance in Escherichia coli. These data indicated that target genes are turned on in a well-defined order with respect to the level of MarA, enabling cells to mount a response that is commensurate to the level of threat detected in the environment. Here we develop a computational model to yield insight into how MarA turns on its target genes. The modeling suggests that MarA can increase the frequency with which a transcript is made while decreasing the overall presence of the transcription machinery at the start of a gene. This mechanism is opposite to the textbook model of transcriptional activation; nevertheless it enables cells to respond quickly to environmental challenges and is likely of general importance for gene regulation in E. coli and beyond. Date: 2009 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1000614 DOI: 10.1371/journal.pcbi.1000614 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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