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Type: Journal article
Title: Positive and negative control of enhancer-promoter interactions by other DNA loops generates specificity and tunability
Author: Hao, N.
Shearwin, K.E.
Dodd, I.B.
Citation: Cell Reports, 2019; 26(9)
Publisher: Cell Press
Issue Date: 2019
ISSN: 2211-1247
Statement of
Nan Hao, Keith E.Shearwin, Ian B.Dodd
Abstract: 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: DNA looping
E. coli
Lac repressor
promoter competition
promoter targeting
sigma-54 promoter
DOI: 10.1016/j.celrep.2019.02.002
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Appears in Collections:Aurora harvest 8
Environment Institute publications

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