title: Target transcription binding sites differentiate two groups of MerR-monovalent metal ion sensors.
abstract: The evolution of bacterial regulatory circuits often involves duplication of genes encoding transcription factors that may suffer both modifications in their detected signals, as well as, rewiring of their target operators. This, and subsequent horizontal gene transfer events contribute to generate a diverse array of regulatory pathways. In Salmonella, two homologous transcription factors CueR and GolS are responsible for Cu and Au sensing and resistance respectively. They share similarities not only in their sequence but also in their target binding sites, although they cluster separately among MerR-monovalent metal sensors. Here, we demonstrate that CueR and GolS can selectively distinguish their target binding sites by recognizing bases at positions 3' and 3 of their cognate operators. Swap of these bases results in switching regulator dependency. The differences in promoter architecture plus the environmentally controlled regulator's cytoplasmic availability warrant intra-regulon regulator-operator selectivity, and the proper response to metal injury. Furthermore, the presence of the distinctive operators' bases is widely extended among the two groups of MerR-monovalent metal sensors, providing evidence of the co-evolution of these factors and their target operators. This approach allows the prediction of regulator's dependency and the identification of transcription modules among groups of homologous transcription factors.
authors.affiliation: Instituto de Biología Molecular, Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Suipacha 531, S2002LRK-Rosario, Argentina.
authors.forename: María E
authors.initials: ME
authors.lastname: Pérez Audero
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Podoroska
authors.forename: María M
authors.initials: MM
authors.lastname: Ibáñez
authors.forename: Ana
authors.initials: A
authors.lastname: Cauerhff
authors.forename: Susana K
authors.initials: SK
authors.lastname: Checa
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Soncini
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D007477:Ions / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D008969:Molecular Sequence Data; D009875:Operator Regions, Genetic; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D007477:Ions; C051124:MerR protein, Bacteria; D008670:Metals; D014157:Transcription Factors