TY - JOUR TI - A system-level model for the microbial regulatory genome. AU - Brooks, Aaron N. AU - Reiss, David J. AU - Allard, Antoine AU - Wu, Wei-Ju AU - Salvanha, Diego M. AU - Plaisier, Christopher L. AU - Chandrasekaran, Sriram AU - Pan, Min AU - Kaur, Amardeep AU - Baliga, Nitin S. T2 - Molecular systems biology AB - 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. DA - 2014/// PY - 2014 VL - 10 SP - 740 J2 - Mol Syst Biol LA - eng SN - 1744-4292 1744-4292 KW - *Gene Regulatory Networks KW - *Genome, Microbial KW - *Models, Genetic KW - Algorithms KW - EGRIN KW - Escherichia coli/genetics KW - Gene Expression Regulation KW - Genetic Fitness KW - Halobacterium salinarum/genetics KW - Operon KW - Regulatory Elements, Transcriptional KW - Regulon KW - gene regulatory networks KW - systems biology KW - transcriptional regulation ER -