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dc.contributor.authorSaelee, P
dc.contributor.authorKearly, A
dc.contributor.authorNutt, SL
dc.contributor.authorGarrett-Sinha, LA
dc.date.accessioned2020-12-18T03:26:12Z
dc.date.available2020-12-18T03:26:12Z
dc.date.issued2017-04-07
dc.identifier.citationSaelee, P., Kearly, A., Nutt, S. L. & Garrett-Sinha, L. A. (2017). Genome-Wide Identification of Target Genes for the Key B Cell Transcription Factor Ets1. FRONTIERS IN IMMUNOLOGY, 8 (APR), https://doi.org/10.3389/fimmu.2017.00383.
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/11343/255768
dc.description.abstractBACKGROUND: The transcription factor Ets1 is highly expressed in B lymphocytes. Loss of Ets1 leads to premature B cell differentiation into antibody-secreting cells (ASCs), secretion of autoantibodies, and development of autoimmune disease. Despite the importance of Ets1 in B cell biology, few Ets1 target genes are known in these cells. RESULTS: To obtain a more complete picture of the function of Ets1 in regulating B cell differentiation, we performed Ets1 ChIP-seq in primary mouse B cells to identify >10,000-binding sites, many of which were localized near genes that play important roles in B cell activation and differentiation. Although Ets1 bound to many sites in the genome, it was required for regulation of less than 5% of them as evidenced by gene expression changes in B cells lacking Ets1. The cohort of genes whose expression was altered included numerous genes that have been associated with autoimmune disease susceptibility. We focused our attention on four such Ets1 target genes Ptpn22, Stat4, Egr1, and Prdm1 to assess how they might contribute to Ets1 function in limiting ASC formation. We found that dysregulation of these particular targets cannot explain altered ASC differentiation in the absence of Ets1. CONCLUSION: We have identified genome-wide binding targets for Ets1 in B cells and determined that a relatively small number of these putative target genes require Ets1 for their normal expression. Interestingly, a cohort of genes associated with autoimmune disease susceptibility is among those that are regulated by Ets1. Identification of the target genes of Ets1 in B cells will help provide a clearer picture of how Ets1 regulates B cell responses and how its loss promotes autoantibody secretion.
dc.languageEnglish
dc.publisherFRONTIERS MEDIA SA
dc.titleGenome-Wide Identification of Target Genes for the Key B Cell Transcription Factor Ets1
dc.typeJournal Article
dc.identifier.doi10.3389/fimmu.2017.00383
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleFrontiers in Immunology
melbourne.source.volume8
melbourne.source.issueAPR
dc.rights.licenseCC BY
melbourne.elementsid1205833
melbourne.contributor.authorNutt, Stephen
dc.identifier.eissn1664-3224
melbourne.accessrightsOpen Access


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