The role of Ets2 transcription factor in the induction of microRNA-155 by LPS, and its targeting by IL-10.
Item Type:Journal Article
Citation:Quinn 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, 4316-4325
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MicroRNA-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.
Australian Research Council (ARC)
Science Foundation Ireland (SFI)
European Research Council (ERC)
Health Research Board (HRB)
Type of material:Journal Article
Series/Report no:The Journel of Biological Chemistry
Availability:Full text available
Subject (TCD):Immunology, Inflammation & Infection