Ligons, D. L.Tuncer, C.Linowes, B. A.Akcay, I. M.Kurtulus, S.Deniz, E.Arslan, B. A.Cevik, S. I.Keller, H. R.Luckey, M. A.Feigenbaum, L.Möröy, T.Ersahin, T.Atalay, R.Erman, B.Park, J. H.2016-02-082016-02-0820120021-9258http://hdl.handle.net/11693/21307Interleukin-7 receptor α (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα up-regulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα up-regulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is up-regulated in the absence of Gfi1 and down-regulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.EnglishBacterial artificial chromosomesCD8 T lymphocytesDexamethasonesGene transcriptionsGlucocorticoidsGrowth factorIn-vivoInterleukin-7Microarray expressionsReceptor expressionRetroviral transductionT cellsThymocytesTranscriptional repressorsTransgeneTransgenic miceUp-regulationArticle10.1074/jbc.M112.378687