More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli
1 Department of Genetics, University of Osnabrück, Barbarastraβe 11, D-49076 Osnabrück, Germany
2 Helmholtz Centre for Infection Research, Inhoffenstraβe 7, D-38124 Braunschweig, Germany
3 Institute of Technical Chemistry - Life Science, Leibniz University of Hannover, Callinstraβe 5, D-30167 Hannover, Germany
4 Systems Biology/Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, D-07745 Jena, Germany
5 Research Group Genome Analytics, Helmholtz Centre for Infection Research, Inhoffenstraβe 7, D-38124 Braunschweig, Germany
6 Department of Bioinformatics, School of Biology and Pharmaceutics, Ernst-Abbe-Platz 2, Friedrich Schiller University of Jena, D-07743 Jena, Germany
7 Research Group Theoretical Systems Biology, School of Biology and Pharmaceutics, Leutragraben 1, Friedrich Schiller University of Jena, D-07743 Jena, Germany
Citation and License
BMC Systems Biology 2011, 5:197 doi:10.1186/1752-0509-5-197Published: 14 December 2011
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.
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.
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.