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

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Anna Katharina Göhler
  • Öznur Kökpinar
  • Wolfgang Schmidt-Heck
  • Robert Geffers
  • Reinhard Guthke
  • Ursula Rinas
  • Stefan Schuster
  • Knut Jahreis
  • Christoph Kaleta

Organisationseinheiten

Externe Organisationen

  • Universität Osnabrück
  • Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
  • Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V.Hans-Knöll-Institut
  • Friedrich-Schiller-Universität Jena
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Details

OriginalspracheEnglisch
Aufsatznummer197
FachzeitschriftBMC systems biology
Jahrgang5
PublikationsstatusVeröffentlicht - 14 Dez. 2011

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.

ASJC Scopus Sachgebiete

Zitieren

More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli. / Göhler, Anna Katharina; Kökpinar, Öznur; Schmidt-Heck, Wolfgang et al.
in: BMC systems biology, Jahrgang 5, 197, 14.12.2011.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Göhler, AK, Kökpinar, Ö, Schmidt-Heck, W, Geffers, R, Guthke, R, Rinas, U, Schuster, S, Jahreis, K & Kaleta, C 2011, 'More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli', BMC systems biology, Jg. 5, 197. https://doi.org/10.1186/1752-0509-5-197, https://doi.org/10.15488/625
Göhler, A. K., Kökpinar, Ö., Schmidt-Heck, W., Geffers, R., Guthke, R., Rinas, U., Schuster, S., Jahreis, K., & Kaleta, C. (2011). More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli. BMC systems biology, 5, Artikel 197. https://doi.org/10.1186/1752-0509-5-197, https://doi.org/10.15488/625
Göhler AK, Kökpinar Ö, Schmidt-Heck W, Geffers R, Guthke R, Rinas U et al. More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli. BMC systems biology. 2011 Dez 14;5:197. doi: 10.1186/1752-0509-5-197, 10.15488/625
Göhler, Anna Katharina ; Kökpinar, Öznur ; Schmidt-Heck, Wolfgang et al. / More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli. in: BMC systems biology. 2011 ; Jahrgang 5.
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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.",
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T1 - More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli

AU - Göhler, Anna Katharina

AU - Kökpinar, Öznur

AU - Schmidt-Heck, Wolfgang

AU - Geffers, Robert

AU - Guthke, Reinhard

AU - Rinas, Ursula

AU - Schuster, Stefan

AU - Jahreis, Knut

AU - Kaleta, Christoph

N1 - Funding Information: We thank Lucille Schmieding for proof-reading the manuscript. Financial support from the German Ministry of Education and Research (BMBF) within the Jena Centre of Bioinformatics and the FORSYS-Partner program (grant FKZ 0315285) is gratefully acknowledged.

PY - 2011/12/14

Y1 - 2011/12/14

N2 - 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.

AB - 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.

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