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Control of Enhancer-Promoter Contact by Alternative DNA Loops

36 Pages Posted: 17 Nov 2018 Publication Status: Published

See all articles by Nan Hao

Nan Hao

University of Adelaide, School of Biological Sciences, Department of Molecular and Biomedical Science

Keith E. Shearwin

University of Adelaide, School of Biological Sciences, Department of Molecular and Biomedical Science

Ian Dodd

University of Adelaide, School of Biological Sciences, Department of Molecular and Biomedical Science

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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 a model in vivo system, showing that activation is highly sensitive to the enhancer-promoter (E-P) distance in the 300-6000 bp range, and can be regulated positively or negatively by assisting or insulating loops formed by Lac repressor. Two σ54 promoters controlled by the same enhancer compete weakly, and a single LacI loop can produce a 15-fold shift in promoter choice by the enhancer. A combined kinetic-thermodynamic model quantifies loop interactions and reveals that the response to changes in the E-P tether by insulators and other loops is highly tunable. While the NtrC system is sensitive to E-P distance and looping control, other enhancers and promoters may resist such manipulation.

Keywords: enhancer, sigma‐54 promoter, NtrC, DNA looping, insulator, modeling, Lac repressor, gene regulation

Suggested Citation

Hao, Nan and Shearwin, Keith E. and Dodd, Ian, Control of Enhancer-Promoter Contact by Alternative DNA Loops (November 16, 2018). Available at SSRN: https://ssrn.com/abstract=3285806 or http://dx.doi.org/10.2139/ssrn.3285806
This version of the paper has not been formally peer reviewed.

Nan Hao

University of Adelaide, School of Biological Sciences, Department of Molecular and Biomedical Science

No 233 North Terrace
Adelaide, 5005
Australia

Keith E. Shearwin

University of Adelaide, School of Biological Sciences, Department of Molecular and Biomedical Science

No 233 North Terrace
Adelaide, 5005
Australia

Ian Dodd (Contact Author)

University of Adelaide, School of Biological Sciences, Department of Molecular and Biomedical Science ( email )

No 233 North Terrace
Adelaide, 5005
Australia