Cell Reports
Volume 26, Issue 9, 26 February 2019, Pages 2419-2433.e3
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Article
Positive and Negative Control of Enhancer-Promoter Interactions by Other DNA Loops Generates Specificity and Tunability

https://doi.org/10.1016/j.celrep.2019.02.002Get rights and content
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Highlights

  • Effect of DNA distance on NtrC enhancer action implies weak looping to the promoter

  • A LacI DNA loop can target the enhancer to the promoter or cause insulation

  • A single LacI loop can combine targeting and insulation to give promoter specificity

  • Modeling shows sensitivity of enhancer action to control by other loops is tunable

Summary

Enhancers are ubiquitous and critical gene-regulatory elements. However, quantitative understanding of the role of DNA looping in the regulation of enhancer action and specificity is limited. We used the Escherichia coli NtrC enhancer-σ54 promoter system as an in vivo model, finding that NtrC activation is highly sensitive to the enhancer-promoter (E-P) distance in the 300–6,000 bp range. DNA loops formed by Lac repressor were able to strongly regulate enhancer action either positively or negatively, recapitulating promoter targeting and insulation. A single LacI loop combining targeting and insulation produced a strong shift in specificity for enhancer choice between two σ54 promoters. A combined kinetic-thermodynamic model was used to quantify the effect of DNA-looping interactions on promoter activity and revealed that sensitivity to E-P distance and to control by other loops is itself dependent on enhancer and promoter parameters that may be subject to regulation.

Keywords

enhancer
sigma-54 promoter
E. coli
NtrC
DNA looping
Lac repressor
promoter targeting
insulator
promoter competition
modeling

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