CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1
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
2012Source 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
ArticleItem Usage Stats
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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 chromosomesCD8 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