|Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states.
|Year of Publication
|B.K. Cho; D. Kim; E.M. Knight; K. Zengler; B.O. Palsson
|PLoS Comput Biol
|BACKGROUND: At the beginning of the transcription process, the RNAP core enzyme requires a sigma-factor to recognize the genomic location where the process initiates. Although the critical role of sigma-factors has been long 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 sigma-factor-promoter interactions in Escherichia coli. The reconstructed network includes 4,724 sigma-factor-specific promoters corresponding to transcription units (TU), representing more than a 300% increase over what has been previously. The reconstructed network was used to investigate competition between alternative sigma-factors the sigma70 and sigma38 regulons, confirming the competition model of sigma substitution and a negative regulation by alternative sigma-factors. Comparison to sigma-factor binding in Klebsiella pneumoniae shows that transcriptional regulation of conserved genes in closely related species is surprisingly divergent.Conclusoins: The reconstructed network reveals 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.