YedVW is one of the uncharacterized two-component systems (TCSs) of . In order to identify the regulation targets of YedVW, we performed genomic SELEX (systematic evolution of ligands by exponential enrichment) screening using phosphorylated YedW and an DNA library, and identified YedW-binding sites within three intergenic spacers, , and , along the genome. Using a reporter assay system, we found that transcription of encoding 5-hydroxyisourate hydrolase, was induced at high concentrations of either Cu or HO. Cu-dependent expression of was observed in the knockout mutant, but was reduced markedly in the -null mutant. However, HO-induced expression was observed in the -null mutant, but not in the -null mutant. Gel mobility shift and DNase I footprinting analyses showed binding of both YedW and CusR to essentially the same sequence within the promoter region. Taken together, we concluded that YedVW and CusSR formed a unique cooperative TCS pair by recognizing and regulating the same targets, but under different environmental conditions – YedVW played a role in HO response regulation, whilst CusSR played a role in Cu response regulation.


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