title: Genome-scale analysis reveals a role for NdgR in the thiol oxidative stress response in Streptomyces coelicolor.
abstract: BACKGROUND
  NdgR is an IclR-type transcription factor that regulates leucine biosynthesis and other metabolic pathways in Streptomyces coelicolor. Recent study revealed that NdgR is one of the regulatory targets of SigR, an oxidative stress response sigma factor, suggesting that the NdgR plays an important physiological role in response to environmental stresses. Although the regulatory functions of NdgR were partly characterized, determination of its regulon is required for better understanding of the transcriptional regulatory network related with the oxidative stress response.
  
  
  RESULTS
  We determined genome-wide binding loci of NdgR by using chromatin immunoprecipitation coupled with sequencing (ChIP-seq) and explored its physiological roles. The ChIP-seq profiles revealed 19 direct binding loci with a 15-bp imperfect palindromic motif, including 34 genes in their transcription units. Most genes in branched-chain amino acid and cysteine biosynthesis pathways were involved in the NdgR regulon. We proved that ndgR is induced by SigR under the thiol oxidation, and that an ndgR mutant strain is sensitive to the thiol oxidizing agent, diamide. Through the expression test of NdgR and the target genes for NdgR under diamide treatment, regulatory motifs were suggested. Interestingly, NdgR constitutes two regulatory motifs, coherent and incoherent feed-forward loops (FFL), in order to control its regulon under the diamide treatment. Using the regulatory motifs, NdgR regulates cysteine biosynthesis in response to thiol oxidative stress, enabling cells to maintain sulfur assimilation with homeostasis under stress conditions.
  
  
  CONCLUSIONS
  Our analysis revealed that NdgR is a global transcriptional regulator involved in the regulation of branched-chain amino acids biosynthesis and sulphur assimilation. The identification of the NdgR regulon broadens our knowledge regarding complex regulatory networks governing amino acid biosynthesis in the context of stress responses in S. coelicolor.
authors.affiliation: School of Chemical and Biological Engineering, Institute of Molecular Biology and Genetics, and Bioengineering Institute, Seoul National University, Seoul, Korea. realkjw1@snu.ac.kr.
authors.forename: Ji-Nu
authors.initials: JN
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences and KAIST institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Korea. mist@kaist.ac.kr.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, 151-742, Korea. secret05@snu.ac.kr.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, 151-742, Korea. jhroe@snu.ac.kr.
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Roe
authors.affiliation: Department of Biological Sciences and KAIST institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, Korea. bcho@kaist.ac.kr.
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Cho
authors.affiliation: School of Chemical and Biological Engineering, Institute of Molecular Biology and Genetics, and Bioengineering Institute, Seoul National University, Seoul, Korea. byungkim@snu.ac.kr.
authors.forename: Byung-Gee
authors.initials: BG
authors.lastname: Kim
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D016680:Genome, Bacterial; D018384:Oxidative Stress / Q000187:drug effects*; D016415:Sequence Alignment; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000235:genetics*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; D001426:Bacterial Proteins; D012808:Sigma Factor; D013438:Sulfhydryl Compounds; D014157:Transcription Factors