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dc.contributor.authorO'NEILL, LUKEen
dc.contributor.authorMCCOY, CLAIREen
dc.contributor.authorQUINN, SUSANen
dc.date.accessioned2014-03-26T10:25:55Z
dc.date.available2014-03-26T10:25:55Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationQuinn SR, Mangan NE, Caffrey BE, Gantier MP, Williams BR, Hertzog PJ, McCoy CE, O'Neill LA., The role of Ets2 transcription factor in the induction of microRNA-155 by LPS, and its targeting by IL-10., The Journel of Biological Chemistry, 289, 9, 2014, 4316-4325en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/68353
dc.descriptionPUBLISHEDen
dc.description.abstractMicroRNA-155 (miR-155) is highly expressed in many cancers such as B cell lymphomas and myeloid leukaemia, and inflammatory disorders such as rheumatoid arthritis, atopic dermatitis and multiple sclerosis. The role of miR- 155 as both a promoter of inflammation and an oncogenic agent provides a clear need for miR-155 itself to be stringently regulated. We therefore investigated the transcriptional regulation of miR-155 in response to the respective pro- and antiinflammatory mediators LPS and IL-10. Bioinformatic analysis revealed Ets binding sites on the miR-155 promoter, and we found that Ets2 is critical for miR- 155 induction by LPS. Truncation and mutational analysis of the miR-155 promoter confirmed the role of the Ets2 binding site proximal to the transcription start site for LPS responsiveness. We observed increased binding of Ets2 to the miR-155 promoter and Ets2 deficient mice displayed decreased induction of miR-155 in response to LPS. IL-10 inhibited the induction of Ets2 mRNA and protein by LPS, thereby decreasing Ets2 function on the pri-155 promoter. We have thus identified Ets2 as a key novel regulator in both the positive and negative control of miR-155 in the inflammatory response.en
dc.description.sponsorshipScience Foundation Ireland (SFI), Health Research Board (HRB)/Marie Curie CoFund, and the European Research Council (ERC) are gratefully acknowledged for funding this work based in Ireland. Monash Institute of Medical Research funding is by the Australian National Health and Medical Research Council, Australian Research Council, HRB/Marie Curie CoFund, and the Victorian Government's Operational Infrastructure Support Program. We would also like to acknowledge Erik Flemington for providing Pri-155 promoter constructs.en
dc.format.extent4316-4325en
dc.language.isoenen
dc.relation.ispartofseriesThe Journel of Biological Chemistryen
dc.relation.ispartofseries289en
dc.relation.ispartofseries9en
dc.rightsYen
dc.subjectMicroRNA-155en
dc.titleThe role of Ets2 transcription factor in the induction of microRNA-155 by LPS, and its targeting by IL-10.en
dc.typeJournal Articleen
dc.contributor.sponsorAustralian Research Council (ARC)en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorEuropean Research Council (ERC)en
dc.contributor.sponsorHealth Research Board (HRB)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/laoneillen
dc.identifier.rssinternalid91284en
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M113.522730en
dc.rights.ecaccessrightsOpenAccess
dc.subject.TCDThemeImmunology, Inflammation & Infectionen


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