In most bacteria, zinc depletion is sensed by Zur, whereas the surplus is sensed by different regulators to achieve zinc homeostasis. Here we present evidence that zinc-bound Zur not only represses genes for zinc acquisition but also induces the zitB gene encoding a zinc exporter in Streptomyces coelicolor, a model actinobacteria. Zinc-dependent gene regulation by Zur occurs in two phases. At sub-femtomolar zinc concentrations (phase I), dimeric Zur binds to the Zur-box motif immediately upstream of the zitB promoter, resulting in low zitB expression. At the same time, Zur represses genes for zinc uptake. At micromolar zinc concentrations (phase II), oligomeric Zur binding with footprint expansion upward from the Zur box results in high zitB induction. Our findings reveal a mode of zinc-dependent gene activation that uses a single metalloregulator to control genes for both uptake and export over a wide range of zinc concentrations.
Bibliographical noteFunding Information:
We are indebted to Drs Yann Dufour and Tim Donohue (UW-Madison) for providing microarrays and assistance in bioinformatics analysis. We thank E.-J. Woo for help in refining model structures. This work was supported by a grant (2014R1A2A1A01002846) from the Ministry of Science, ICT and Future Planning and a grant (2011-0031960) for Intelligent Synthetic Biology Center of Global Frontier Project to J.-H.R.; S.-H.C. was supported by BK21-Plus fellowship for graduate students for Biological Sciences at SNU.
© The Author(s) 2017.