Positive and Negative Control of Enhancer-Promoter Interactions by Other DNA Loops Generates Specificity and Tunability

Cell Reports
Nan HaoIan 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.

Citations

Nov 12, 2019·Briefings in Functional Genomics·Surya K Ghosh, Daniel Jost
Apr 7, 2020·Science China. Life Sciences·Mengfan LiCheng Li
Jul 16, 2020·Cells·Oleg V BylinoYulii V Shidlovskii
Feb 10, 2021·Nature Reviews. Genetics·Haifeng WangLei S Qi
Jan 30, 2021·Nucleic Acids Research·Nan HaoIan B Dodd
May 8, 2021·Nature Genetics·Di ZhangGerd A Blobel
Jun 18, 2021·Cell Systems·Nika ShakibaDomitilla Del Vecchio
Mar 31, 2021·Annual Review of Biochemistry·Max A EnglishJames J Collins
Jul 1, 2021·ACS Synthetic Biology·Nan HaoKeith E Shearwin

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