Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/118914
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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):2419-2433.e1–e3 |
Publisher: | Cell Press |
Issue Date: | 2019 |
ISSN: | 2211-1247 2211-1247 |
Statement of Responsibility: | 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 |
Rights: | © 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
DOI: | 10.1016/j.celrep.2019.02.002 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1100651 http://purl.org/au-research/grants/arc/DE150100091 http://purl.org/au-research/grants/arc/DP160101450 |
Published version: | http://dx.doi.org/10.1016/j.celrep.2019.02.002 |
Appears in Collections: | Aurora harvest 8 Molecular and Biomedical Science publications |
Files in This Item:
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hdl_118914.pdf | Published version | 2.49 MB | Adobe PDF | View/Open |
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