title: More than just a metabolic regulator--elucidation and validation of new targets of PdhR in Escherichia coli.
abstract: BACKGROUND
  The pyruvate dehydrogenase regulator protein (PdhR) of Escherichia coli acts as a transcriptional regulator in a pyruvate dependent manner to control central metabolic fluxes. However, the complete PdhR regulon has not yet been uncovered. To achieve an extended understanding of its gene regulatory network, we combined large-scale network inference and experimental verification of results obtained by a systems biology approach.
  
  
  RESULTS
  22 new genes contained in two operons controlled by PdhR (previously only 20 regulatory targets in eight operons were known) were identified by analysing a large-scale dataset of E. coli from the Many Microbes Microarray Database and novel expression data from a pdhR knockout strain, as well as a PdhR overproducing strain. We identified a regulation of the glycolate utilization operon glcDEFGBA using chromatin immunoprecipitation and gel shift assays. We show that this regulation could be part of a cross-induction between genes necessary for acetate and pyruvate utilisation controlled through PdhR. Moreover, a link of PdhR regulation to the replication machinery of the cell via control of the transcription of the dcw-cluster was verified in experiments. This augments our knowledge of the functions of the PdhR-regulon and demonstrates its central importance for further cellular processes in E. coli.
  
  
  CONCLUSIONS
  We extended the PdhR regulon by 22 new genes contained in two operons and validated the regulation of the glcDEFGBA operon for glycolate utilisation and the dcw-cluster for cell division proteins experimentally. Our results provide, for the first time, a plausible regulatory link between the nutritional status of the cell and cell replication mediated by PdhR.
authors.affiliation: Department of Genetics, University of Osnabrück, Osnabrück, Germany.
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Göhler
authors.forename: Öznur
authors.initials: Ö
authors.lastname: Kökpinar
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmidt-Heck
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.forename: Ursula
authors.initials: U
authors.lastname: Rinas
authors.forename: Stefan
authors.initials: S
authors.lastname: Schuster
authors.forename: Knut
authors.initials: K
authors.lastname: Jahreis
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaleta
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D005798:Genes, Bacterial; D053858:Metabolic Networks and Pathways; D018085:Regulon / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D049490:Systems Biology / Q000379:methods
chemical_list: D029968:Escherichia coli Proteins; C084955:PdhR protein, E coli; D012097:Repressor Proteins