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      • Department of Molecular Biology and Genetics
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      CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1

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      Author
      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.
      Date
      2012
      Source Title
      Journal of Biological Chemistry
      Print ISSN
      0021-9258
      Publisher
      The American Society for Biochemistry and Molecular Biology, Inc.
      Volume
      287
      Issue
      41
      Pages
      34386 - 34399
      Language
      English
      Type
      Article
      Item Usage Stats
      116
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      87
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      Abstract
      Interleukin-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.
      Keywords
      Bacterial artificial chromosomes
      CD8 T lymphocytes
      Dexamethasones
      Gene transcriptions
      Glucocorticoids
      Growth factor
      In-vivo
      Interleukin-7
      Microarray expressions
      Receptor expression
      Retroviral transduction
      T cells
      Thymocytes
      Transcriptional repressors
      Transgene
      Transgenic mice
      Up-regulation
      Permalink
      http://hdl.handle.net/11693/21307
      Published Version (Please cite this version)
      http://dx.doi.org/10.1074/jbc.M112.378687
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