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

• DOI: 10.1016/j.celrep.2019.02.002
• Publication Date: 2019-02-26T10:42:52Z
• Authors: Nan Hao; Keith E. Shearwin; Ian B. Dodd
• Keywords: Lac repressor; Enhancer RNAs; Enhancer trap

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