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|Title:||Positive and negative control of enhancer-promoter interactions by other DNA loops generates specificity and tunability|
|Citation:||Cell Reports, 2019; 26(9)|
|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; NtrC; enhancer; insulator; modeling; promoter competition; promoter targeting; sigma-54 promoter|
|Appears in Collections:||Environment Institute publications|
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