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Open Access Research article

Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states

Byung-Kwan Cho12, Donghyuk Kim1, Eric M Knight1, Karsten Zengler1 and Bernhard O Palsson13*

  • * Corresponding author: Bernhard O Palsson palsson@ucsd.edu

  • † Equal contributors

Author Affiliations

1 Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA

2 Current address: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-751, Republic of Korea

3 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark

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BMC Biology 2014, 12:4  doi:10.1186/1741-7007-12-4

Published: 24 January 2014

Abstract

Background

At the beginning of the transcription process, the RNA polymerase (RNAP) core enzyme requires a σ-factor to recognize the genomic location at which the process initiates. Although the crucial role of σ-factors has long been appreciated and characterized for many individual promoters, we do not yet have a genome-scale assessment of their function.

Results

Using multiple genome-scale measurements, we elucidated the network of σ-factor and promoter interactions in Escherichia coli. The reconstructed network includes 4,724 σ-factor-specific promoters corresponding to transcription units (TUs), representing an increase of more than 300% over what has been previously reported. The reconstructed network was used to investigate competition between alternative σ-factors (the σ70 and σ38 regulons), confirming the competition model of σ substitution and negative regulation by alternative σ-factors. Comparison with σ-factor binding in Klebsiella pneumoniae showed that transcriptional regulation of conserved genes in closely related species is unexpectedly divergent.

Conclusions

The reconstructed network reveals the regulatory complexity of the promoter architecture in prokaryotic genomes, and opens a path to the direct determination of the systems biology of their transcriptional regulatory networks.

Keywords:
Escherichia coli; Sigma factor; Network reconstruction; Comparative analysis; Klebsiella pneumoniae; Omics data; Systems biology