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dc.contributor.authorDORMAN, CHARLESen
dc.date.accessioned2014-09-24T13:40:56Z
dc.date.available2014-09-24T13:40:56Z
dc.date.issued2012en
dc.date.submitted2012en
dc.identifier.citationCameron ADS, Dorman CJ, A fundamental regulatory mechanism operating through OmpR and DNA topology controls expression of Salmonella pathogenicity islands SPI-1 and SPI-2, PLoS Genetics, 8, 3, 2012, e1002615en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/71400
dc.descriptionPUBLISHEDen
dc.descriptionPublished online 22 March 2012en
dc.description.abstractDNA topology has fundamental control over the ability of transcription factors to access their target DNA sites at gene promoters. However, the influence of DNA topology on protein–DNA and protein–protein interactions is poorly understood. For example, relaxation of DNA supercoiling strongly induces the well-studied pathogenicity gene ssrA (also called spiR) in Salmonella enterica, but neither the mechanism nor the proteins involved are known. We have found that relaxation of DNA supercoiling induces expression of the Salmonella pathogenicity island (SPI)-2 regulator ssrA as well as the SPI-1 regulator hilC through a mechanism that requires the two-component regulator OmpR-EnvZ. Additionally, the ompR promoter is autoregulated in the same fashion. Conversely, the SPI-1 regulator hilD is induced by DNA relaxation but is repressed by OmpR. Relaxation of DNA supercoiling caused an increase in OmpR binding to DNA and a concomitant decrease in binding by the nucleoid-associated protein FIS. The reciprocal occupancy of DNA by OmpR and FIS was not due to antagonism between these transcription factors, but was instead a more intrinsic response to altered DNA topology. Surprisingly, DNA relaxation had no detectable effect on the binding of the global repressor H-NS. These results reveal the underlying molecular mechanism that primes SPI genes for rapid induction at the onset of host invasion. Additionally, our results reveal novel features of the archetypal two-component regulator OmpR. OmpR binding to relaxed DNA appears to generate a locally supercoiled state, which may assist promoter activation by relocating supercoiling stress-induced destabilization of DNA strands. Much has been made of the mechanisms that have evolved to regulate horizontally-acquired genes such as SPIs, but parallels among the ssrA, hilC, and ompR promoters illustrate that a fundamental form of regulation based on DNA topology coordinates the expression of these genes regardless of their origins.en
dc.format.extente1002615en
dc.language.isoenen
dc.relation.ispartofseriesPLoS Geneticsen
dc.relation.ispartofseries8en
dc.relation.ispartofseries3en
dc.rightsYen
dc.subjectDNAen
dc.subjectDNA transcriptionen
dc.subjectDNA-binding proteinsen
dc.subjectGene expressionen
dc.subjectPolymerase chain reactionen
dc.subjectSalmonella entericaen
dc.subjectTopologyen
dc.titleA fundamental regulatory mechanism operating through OmpR and DNA topology controls expression of Salmonella pathogenicity islands SPI-1 and SPI-2en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/cjdormanen
dc.identifier.rssinternalid77928en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1002615en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber07/IN1/B918en
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.rssurihttp://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002615#pgen.1002615.s002en


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