title: Predicting the impact of promoter variability on regulatory outputs.
abstract: The increased availability of whole genome sequences calls for quantitative models of global gene expression, yet predicting gene expression patterns directly from genome sequence remains a challenge. We examine the contributions of an individual regulator, the ferrous iron-responsive regulatory element, BqsR, on global patterns of gene expression in Pseudomonas aeruginosa. The position weight matrix (PWM) derived for BqsR uncovered hundreds of likely binding sites throughout the genome. Only a subset of these potential binding sites had a regulatory consequence, suggesting that BqsR/DNA interactions were not captured within the PWM or that the broader regulatory context at each promoter played a greater role in setting promoter outputs. The architecture of the BqsR operator was systematically varied to understand how binding site parameters influence expression. We found that BqsR operator affinity was predicted by the PWM well. At many promoters the surrounding regulatory context, including overlapping operators of BqsR or the presence of RhlR binding sites, were influential in setting promoter outputs. These results indicate more comprehensive models that include local regulatory contexts are needed to develop a predictive understanding of global regulatory outputs.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.|Department of Chemistry, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Naomi N
authors.initials: NN
authors.lastname: Kreamer
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.|Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Phillips
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.|Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Dianne K
authors.initials: DK
authors.lastname: Newman
authors.affiliation: Department of Physics and Astronomy, University of Southern California, Los Angeles, CA 90089, USA.|Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: James Q
authors.initials: JQ
authors.lastname: Boedicker
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial / Q000235:genetics; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D005296:Ferrous Compounds