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More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265435/ https://www.ncbi.nlm.nih.gov/pubmed/22168595 http://dx.doi.org/10.1186/1752-0509-5-197 |
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author | Göhler, Anna-Katharina Kökpinar, Öznur Schmidt-Heck, Wolfgang Geffers, Robert Guthke, Reinhard Rinas, Ursula Schuster, Stefan Jahreis, Knut Kaleta, Christoph |
author_facet | Göhler, Anna-Katharina Kökpinar, Öznur Schmidt-Heck, Wolfgang Geffers, Robert Guthke, Reinhard Rinas, Ursula Schuster, Stefan Jahreis, Knut Kaleta, Christoph |
author_sort | Göhler, Anna-Katharina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3265435 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32654352012-01-25 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 Geffers, Robert Guthke, Reinhard Rinas, Ursula Schuster, Stefan Jahreis, Knut Kaleta, Christoph BMC Syst Biol Research Article 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. BioMed Central 2011-12-14 /pmc/articles/PMC3265435/ /pubmed/22168595 http://dx.doi.org/10.1186/1752-0509-5-197 Text en Copyright ©2011 Göhler et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Göhler, Anna-Katharina Kökpinar, Öznur Schmidt-Heck, Wolfgang Geffers, Robert Guthke, Reinhard Rinas, Ursula Schuster, Stefan Jahreis, Knut Kaleta, Christoph More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli |
title | More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli |
title_full | More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli |
title_fullStr | More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli |
title_full_unstemmed | More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli |
title_short | More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli |
title_sort | more than just a metabolic regulator - elucidation and validation of new targets of pdhr in escherichia coli |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265435/ https://www.ncbi.nlm.nih.gov/pubmed/22168595 http://dx.doi.org/10.1186/1752-0509-5-197 |
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