Operator discrimination between paralog MerR regulators in Salmonella

SONCINI, F. C.

Tucson

Simposio; BioMetals 2010 (7th International Biometals Symposium); 2010

All cells possess a battery of highly specific regulatory proteins that control metal ions homeostasis by modulating the balance of intake/efflux of a particular metal ion. This control is fundamental to guarantee the acquisition of the required amount of essential metals and at the same time to avoid toxicity caused either by their overload or by the presence of toxic metals. In Salmonella, two highly homologous transcription factors CueR and GolS are responsible for sensing and resistance to Cu and Au, respectively. They share similarities not only in their sequence but also in their promoter target binding sites and their regulated genes. Although highly homologous, phylogenetic analysis shows that these two proteins cluster separately among monovalent metal ion MerR sensors. The differences between these two transcriptional regulators are extended to their target transcription binding sites. Indeed, these regulators can distinguish operators by recognizing specific nucleotide bases at the promoter region of their target genes. Promoter architecture plus the environmentally-controlled regulator’s cytoplasmic availability warrant in vivo regulator-operator selectivity, and the proper response to metal injury. The distinction in target transcription binding sites is widely extended among GolS- and CueR-like factors present in Gram negative species. This approach allows the identification of genes under the control of these transcription factors and the prediction of transcription modules among these groups of highly homologous MerR monovalent metal ion regulators in yet uncharacterized bacterial species.