title: Competition between the GlnR and PhoP regulators for the glnA and amtB promoters in Streptomyces coelicolor.
abstract: Interaction of regulatory networks is a subject of great interest in systems biology of bacteria. Phosphate control of metabolism in Streptomyces is mediated by the two-component system PhoR-PhoP. Similarly, the utilization of different nitrogen sources is controlled by the regulator GlnR. Transcriptomic and biochemical analysis revealed that glnA (encoding a glutamine synthetase), glnR and other nitrogen metabolism genes are under PhoP control. DNA-binding experiments showed that PhoP binds to other nitrogen-regulated genes (SCO0255, SCO01863 and ureA). Using the glnA promoter as model, we observed that PhoP and GlnR compete for binding to the same promoter region, showing GlnR a higher affinity. Using a total of 14 GlnR-binding sites (50 direct repeat units) we established two information-based models that describe the GlnR box as consisting of two 11-nt direct repeats each with clear differences to PHO box. DNA-binding studies with different mutant sequences of glnA promoter revealed that the sequence recognized by GlnR is found in the coding strand whereas that recognized by PhoP is overlapping in the non-coding strand. In amtB promoter PhoP and GlnR boxes are not totally overlapping and both proteins bind simultaneously. PhoP control of nitrogen metabolism genes helps to balance the cellular P/N equilibrium.
authors.affiliation: INBIOTEC, Instituto de Biotecnología de León, Avda. Real n°. 1, Parque Científico de León, 24006 León, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sola-Landa
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez-García
authors.forename: Rafat
authors.initials: R
authors.lastname: Amin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.forename: Juan F
authors.initials: JF
authors.lastname: Martín
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D027682:Cation Transport Proteins / Q000235:genetics*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics*; D016296:Mutagenesis; D009584:Nitrogen / Q000378:metabolism; D009875:Operator Regions, Genetic; D011401:Promoter Regions, Genetic; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C082451:GlnR protein, Streptomyces coelicolor; D015534:Trans-Activators; C061064:PhoP protein, Bacteria; C081173:glutamine synthetase I; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen