Cho, Byung-Kwan3; Kim, Donghyuk3; Knight, Eric M.3; Zengler, Karsten1; Palsson, Bernhard1
1 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2 Network Reconstruction in Silico Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3 University of California
Background: At the beginning of the transcription process, the RNA polymerase (RNAP) core enzyme requires a sigma-factor to recognize the genomic location at which the process initiates. Although the crucial role of sigma-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 s-factor and promoter interactions in Escherichia coli. The reconstructed network includes 4,724 sigma-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 sigma-factors (the sigma(70) and sigma(38) regulons), confirming the competition model of sigma substitution and negative regulation by alternative s-factors. Comparison with sigma-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.
Journal of Biology (online), 2014, Vol 12, Issue 4