Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/100280
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Type: Journal article
Title: The role of repressor kinetics in relief of transcriptional interference between convergent promoters
Author: Hao, N.
Palmer, A.
Ahlgren-Berg, A.
Shearwin, K.
Dodd, I.
Citation: Nucleic Acids Research, 2016; 44(14):6625-6638
Publisher: Oxford University Press
Issue Date: 2016
ISSN: 0305-1048
1362-4962
Statement of
Responsibility: 
Nan Hao, Adam C. Palmer, Alexandra Ahlgren-Berg, Keith E. Shearwin, and Ian B. Dodd
Abstract: Transcriptional interference (TI), where transcription from a promoter is inhibited by the activity of other promoters in its vicinity on the same DNA, enables transcription factors to regulate a target promoter indirectly, inducing or relieving TI by controlling the interfering promoter. For convergent promoters, stochastic simulations indicate that relief of TI can be inhibited if the repressor at the interfering promoter has slow binding kinetics, making it either sensitive to frequent dislodgement by elongating RNA polymerases (RNAPs) from the target promoter, or able to be a strong roadblock to these RNAPs. In vivo measurements of relief of TI by CI or Cro repressors in the bacteriophage λ PR-PRE system show strong relief of TI and a lack of dislodgement and roadblocking effects, indicative of rapid CI and Cro binding kinetics. However, repression of the same λ promoter by a catalytically dead CRISPR Cas9 protein gave either compromised or no relief of TI depending on the orientation at which it binds DNA, consistent with dCas9 being a slow kinetics repressor. This analysis shows how the intrinsic properties of a repressor can be evolutionarily tuned to set the magnitude of relief of TI.
Keywords: Bacteriophage lambda; DNA-Directed RNA Polymerases; Transcription Factors; Repressor Proteins; Stochastic Processes; Transcription, Genetic; Kinetics; Models, Molecular; Viral Regulatory and Accessory Proteins; Promoter Regions, Genetic; CRISPR-Associated Proteins
Rights: © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
RMID: 0030050444
DOI: 10.1093/nar/gkw600
Grant ID: http://purl.org/au-research/grants/arc/DE150100091
http://purl.org/au-research/grants/arc/DP110101470
http://purl.org/au-research/grants/arc/DP150103009
http://purl.org/au-research/grants/nhmrc/1100651
Appears in Collections:Biochemistry publications

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