A system-level model for the microbial regulatory genome

Aaron N. Brooks, David J. Reiss, Antoine Allard, Wei Ju Wu, Diego M. Salvanha, Christopher L. Plaisier, Sriram Chandrasekaran, Min Pan, Amardeep Kaur, Nitin S. Baliga

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish (US)
Article number740
JournalMolecular Systems Biology
Issue number7
StatePublished - Jul 2014
Externally publishedYes


  • gene regulatory networks
  • systems biology
  • transcriptional regulation

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • Information Systems
  • Applied Mathematics
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Computational Theory and Mathematics


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