The role of repressor kinetics in relief of transcriptional interference between convergent promoters

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dc.contributor.authorHao, N.
dc.contributor.authorPalmer, A.
dc.contributor.authorAhlgren-Berg, A.
dc.contributor.authorShearwin, K.
dc.contributor.authorDodd, I.
dc.date.issued2016
dc.description.abstractTranscriptional 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.
dc.description.statementofresponsibilityNan Hao, Adam C. Palmer, Alexandra Ahlgren-Berg, Keith E. Shearwin, and Ian B. Dodd
dc.identifier.citationNucleic Acids Research, 2016; 44(14):6625-6638
dc.identifier.doi10.1093/nar/gkw600
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.orcidHao, N. [0000-0001-5836-3507]
dc.identifier.orcidShearwin, K. [0000-0002-7736-2742]
dc.identifier.orcidDodd, I. [0000-0003-2969-6841]
dc.identifier.urihttp://hdl.handle.net/2440/100280
dc.language.isoen
dc.publisherOxford University Press
dc.relation.granthttp://purl.org/au-research/grants/arc/DE150100091
dc.relation.granthttp://purl.org/au-research/grants/arc/DP110101470
dc.relation.granthttp://purl.org/au-research/grants/arc/DP150103009
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1100651
dc.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
dc.source.urihttps://doi.org/10.1093/nar/gkw600
dc.subjectBacteriophage lambda
dc.subjectDNA-Directed RNA Polymerases
dc.subjectTranscription Factors
dc.subjectRepressor Proteins
dc.subjectStochastic Processes
dc.subjectTranscription, Genetic
dc.subjectKinetics
dc.subjectModels, Molecular
dc.subjectViral Regulatory and Accessory Proteins
dc.subjectPromoter Regions, Genetic
dc.subjectCRISPR-Associated Proteins
dc.titleThe role of repressor kinetics in relief of transcriptional interference between convergent promoters
dc.typeJournal article
pubs.publication-statusPublished

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