Details
| Original language | English |
|---|---|
| Article number | 197 |
| Journal | BMC systems biology |
| Volume | 5 |
| Publication status | Published - 14 Dec 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 subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Structural Biology
- Mathematics(all)
- Modelling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Computer Science(all)
- Computer Science Applications
- Mathematics(all)
- Applied Mathematics
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In: BMC systems biology, Vol. 5, 197, 14.12.2011.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=84856228299&partnerID=8YFLogxK
U2 - 10.1186/1752-0509-5-197
DO - 10.1186/1752-0509-5-197
M3 - Article
C2 - 22168595
AN - SCOPUS:84856228299
VL - 5
JO - BMC systems biology
JF - BMC systems biology
SN - 1752-0509
M1 - 197
ER -