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Predicting the impact of promoter variability on regulatory outputs

Kreamer, Naomi N. and Phillips, Rob and Newman, Dianne K. and Boedicker, James Q. (2015) Predicting the impact of promoter variability on regulatory outputs. Scientific Reports, 5 . Art. No. 18238. ISSN 2045-2322. PMCID PMC4682146.

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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.

Item Type:Article
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URLURL TypeDescription Information CentralArticle
Phillips, Rob0000-0003-3082-2809
Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2015 Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit Received: 27 August 2015, Accepted: 16 November 2015. Published: 17 December 2015. This work was supported by the National Institutes of Health, grant numbers DP1 OD000217, (Directors Pioneer Award), 5R01HL117328-03, R01 GM085286 and R01 GM085286B, and 1 U54 CA143869 (Northwestern PSOC Center); La Fondation Pierre Gilles de Gennes (R.P.); the Center for Microbial Interactions at Caltech (J.B.). D.K.N. is an HHMI Investigator. Author Contributions: N.K., D.N., R.P. and J.B. conceived and designed the study, N.K. and J.B. performed experiments and analyzed the results, N.K., D.N., R.P. and J.B. all contributed to writing the manuscript. The authors declare no competing financial interests.
Funding AgencyGrant Number
NIHDP1 OD000217A
NIHR01 GM085286
NIHR01 GM085286B
NIH1 U54 CA143869
Caltech Center for Microbial InteractionsUNSPECIFIED
La Fondation Pierre Gilles de GennesUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC4682146
Record Number:CaltechAUTHORS:20160106-065143620
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Official Citation:Kreamer, N. et al. Predicting the impact of promoter variability on regulatory outputs. Sci. Rep. 5, 18238; doi: 10.1038/srep18238 (2015).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63401
Deposited By: Ruth Sustaita
Deposited On:06 Jan 2016 18:12
Last Modified:17 Apr 2020 19:13

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