The activity of each protein is induced by different signals: the activity of Rob is increased with dipyridyl, bile salts, or decanoate [45, 46], and the activities of MarA and SoxS are increased by the aromatic weak acid salicylate [5, 47] and by oxidative stress [31], respectively. SoxS was induced by tellurite (TeO₃^2-) in a DNA microarray analysis [48]. Many genes are regulated by all three proteins; however, some genes are regulated by only one of them. The differential regulation of these genes might be caused by the degeneracy of their DNA-binding sites [49]. SoxS, MarA, and Rob bind as monomers to the same DNA site, a degenerate 20-bp sequence known as the Mar-Sox-Rob box, which has to be in a specific orientation and distance relative to the -35 and -10 boxes of the promoter [3, 50]. In class I promoters, the activators bind upstream of the -35 box and are generally oriented in the backward direction, while in class II promoters the proteins overlap the -35 promoter hexamer and generally are oriented in the forward direction [3, 50]. As a subset of the class I promoters, the Mar-Sox-Rob box is separated by ~30 bp from the -10 hexamer but can be functional in either orientation [3, 50]. The Mar-Sox-Rob box contains an "invariant A" at position 1, two recognition elements, the RE1 at position 4-7 and RE2 at position 15-18, and a 7-bp A/T-rich spacer separating these elements [51, 52, 53]. There are more than 10,000 such binding sites per genome [54]. However, the majority of these sites are not functional because they are not in the proper orientation or distance relative to the promoter [55]. It was proposed that these proteins bind to their target sites by a mechanism named "DNA scanning" or "prerecruitment." In prerecruitment, the protein first binds to RNA polymerase in solution, and the binary complex then scans the DNA to find its binding sites [54, 55]. It has been shown that SoxS binds to the C-terminal domain of the α-subunit of RNA polymerase (α-CTD), in particular, it interacts with amino acid residues lying in or near the DNA-binding determinant of α-CTD. Apparently, SoxS functions as a co-sigma factor and redirects RNA polymerase to promoters carrying a SoxS-binding site [56]. A new interaction that also occurs via prerecruitment between σ⁷⁰ R4 of RNA polymerase (RNAP) and SoxS has been identified [57]. There is evidence for the existence of two types of interactions between SoxS and σ⁷⁰ R4, with one type being able to occur "off-DNA" (within a SoxS-RNAP binary complex that scans the chromosome for SoxS-dependent promoters) and with the other one occurring "on-DNA" (within a SoxS-RNAP binary complex residing at a SoxS-dependent promoter) [57]. SoxS is now the first example of an Escherichia coli transcriptional activator that uses a single positive control surface to make specific protein-protein contacts with two different subunits of RNAP [57]. In class I promoters, the σ⁷⁰ R4 region binds to the -35 box and SoxS binds upstream of the hexamer, but in class II promoters SoxS binds to the -35 box, occluding the binding of σ⁷⁰ R4 [58]. SoxS, MarA, and Rob belong to the AraC/XylS family of transcriptional regulators [59] and, like other members of this family, they have two helix-turn-helix (HTH) motifs for DNA binding: one of them, located in the N-terminal region, interacts with the element RE1 of the Mar-Sox-Rob box, and the HTH located in the C-terminal region interacts with the element RE2 [52, 60, 61]. soxS is divergently transcribed from soxR [62]. SoxR is the transcriptional activator for soxS and a sensor for superoxide and nitric oxide through its [2Fe-2S] center. It activates soxS transcription when oxidized [63, 64]. soxS is regulated only by its intracellular concentration. Upon removal of the inducer, SoxS is degraded by the Lon protease [65]. The binding of SoxS with DNA or RNA polymerase protects it from degradation [66]. Transcriptomic and statistical modeling analyses with Zn concentration shifts showed a transient change in the activity of the iron regulator Fur and of the oxidative stress regulator SoxS; these findings suggest a competitive binding mechanism for the physiology of Zn and Fe uptake [67]. The expression of soxS is not affected by iron limitation [15]. Cadmium prevented the induction of soxRS-controlled protective enzymes by the redox-cycling agent paraquat [68], although this appeared not to be due to specific inactivation of the soxRS regulon and most probably resulted from generalized suppression of protein synthesis [68, 69]. The expression of the gene soxS is enhanced in the presence of a copolymer based on monomethylether poly(ethylene glycol), methyl methacrylate, and 2-dimethyl(aminoethyl) methacrylate [70]. In cells induced for chlorhexidine (CHX) resistance, expression levels of soxS and |FRAME: EG11366| are decreased [71]. Reviews: [31, 72, 73, 74]