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A transcription factor (TF), OmpR, plays a critical role in transcriptional regulation of the osmotic stress response in bacteria. Here, we reveal a genome-scale OmpR regulon in  Escherichia coli  K-12 MG1655. Integrative data analysis reveals that a total of 37 genes in 24 transcription units (TUs) belong to OmpR regulon. Among them, 26 genes show more than two-fold changes in expression level in an OmpR knock-out strain. Specifically, we find that: 1) OmpR regulates mostly membrane-located gene products involved in diverse fundamental biological processes, such as  narU  (encoding nitrate/nitrite transporter),  ompX  (encoding outer membrane protein X), and  nuoN  (encoding NADH:ubiquinone oxidoreductase); 2) by investigating co-regulation of entire sets of genes regulated by other stress-response TFs, stresses are surprisingly independently regulated among each other; and, 3) a detailed investigation of the physiological roles of the newly discovered OmpR regulon genes reveals that activation of  narU  represents a novel strategy to significantly improve osmotic stress tolerance of  E .  coli . Thus, the genome-scale approach to elucidating regulons comprehensively identifies regulated genes and leads to fundamental discoveries related to stress responses.

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Revealing genome-scale transcriptional regulatory landscape of OmpR highlights its expanded regulatory roles under osmotic stress in Escherichia coli K-12 MG1655