Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states.
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.
Byung-Kwan
BK
Cho
Donghyuk
D
Kim
Eric M
EM
Knight
Karsten
K
Zengler
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. palsson@ucsd.edu.
Bernhard O
BO
Palsson
D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D030541:Databases, Genetic; D004926:Escherichia coli / Q000235:genetics*; D053263:Gene Regulatory Networks; D016680:Genome, Bacterial / Q000235:genetics*; D020035:Holoenzymes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018085:Regulon / Q000235:genetics; D012808:Sigma Factor / Q000737:chemistry* / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D020035:Holoenzymes; D012808:Sigma Factor; D012321:DNA-Directed RNA Polymerases