More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli

2.50
Hdl Handle:
http://hdl.handle.net/10033/620710
Title:
More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli
Authors:
Göhler, Anna-Katharina; Kökpinar, Öznur; Schmidt-Heck, Wolfgang; Geffers, Robert; Guthke, Reinhard; Rinas, Ursula; Schuster, Stefan; Jahreis, Knut; Kaleta, Christoph
Abstract:
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.
Citation:
BMC Systems Biology. 2011 Dec 14;5(1):197
Issue Date:
14-Dec-2011
URI:
http://dx.doi.org/10.1186/1752-0509-5-197; http://hdl.handle.net/10033/620710
Type:
Journal Article
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DC FieldValue Language
dc.contributor.authorGöhler, Anna-Katharinaen
dc.contributor.authorKökpinar, Öznuren
dc.contributor.authorSchmidt-Heck, Wolfgangen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorGuthke, Reinharden
dc.contributor.authorRinas, Ursulaen
dc.contributor.authorSchuster, Stefanen
dc.contributor.authorJahreis, Knuten
dc.contributor.authorKaleta, Christophen
dc.date.accessioned2017-01-16T15:30:58Z-
dc.date.available2017-01-16T15:30:58Z-
dc.date.issued2011-12-14en
dc.identifier.citationBMC Systems Biology. 2011 Dec 14;5(1):197en
dc.identifier.urihttp://dx.doi.org/10.1186/1752-0509-5-197en
dc.identifier.urihttp://hdl.handle.net/10033/620710-
dc.description.abstractAbstract 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.en
dc.titleMore than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia colien
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderGöhler et al; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:30:44Zen
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