A system-level model for the microbial regulatory genome

Mol Syst Biol. 2014 Jul 15;10(7):740. doi: 10.15252/msb.20145160.


Microbes can tailor transcriptional responses to diverse environmental challenges despite having streamlined genomes and a limited number of regulators. Here, we present data-driven models that capture the dynamic interplay of the environment and genome-encoded regulatory programs of two types of prokaryotes: Escherichia coli (a bacterium) and Halobacterium salinarum (an archaeon). The models reveal how the genome-wide distributions of cis-acting gene regulatory elements and the conditional influences of transcription factors at each of those elements encode programs for eliciting a wide array of environment-specific responses. We demonstrate how these programs partition transcriptional regulation of genes within regulons and operons to re-organize gene-gene functional associations in each environment. The models capture fitness-relevant co-regulation by different transcriptional control mechanisms acting across the entire genome, to define a generalized, system-level organizing principle for prokaryotic gene regulatory networks that goes well beyond existing paradigms of gene regulation. An online resource (http://egrin2.systemsbiology.net) has been developed to facilitate multiscale exploration of conditional gene regulation in the two prokaryotes.

Keywords: EGRIN; gene regulatory networks; systems biology; transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Escherichia coli / genetics
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Genetic Fitness
  • Genome, Microbial*
  • Halobacterium salinarum / genetics
  • Models, Genetic*
  • Operon
  • Regulatory Elements, Transcriptional
  • Regulon