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CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1.

ABSTRACT: Interleukin-7 receptor ? (IL-7R?) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7R? 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-7R? 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-7R? 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-7R? 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.

SUBMITTER: Ligons DL

PROVIDER: S-EPMC3464544 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1.

Ligons Davinna L DL Tuncer Ceren C Linowes Brett A BA Akcay Izzet Mehmet IM Kurtulus Sema S Deniz Emre E Atasever Arslan Belkis B Cevik Safak Isil SI Keller Hilary R HR Luckey Megan A MA Feigenbaum Lionel L Möröy Tarik T Ersahin Tulin T Atalay Rengul R Erman Batu B Park Jung-Hyun JH

The Journal of biological chemistry 20120803 41

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 transduc ...[more]

PMID: 22865857

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Project description:The LH surge triggers dramatic transcriptional changes in genes associated with ovulation and luteinization. The present study investigated the spatiotemporal expression of nuclear factor IL-3 (NFIL3), a transcriptional regulator of the basic leucine zipper transcription factor superfamily, and its potential role in the ovary during the periovulatory period. Immature female rats were injected with pregnant mare's serum gonadotropin, treated with human chorionic gonadotropin (hCG), and ovaries or granulosa cells were collected at various times after hCG. Nfil3 mRNA was highly induced both in intact ovaries and granulosa cells after hCG treatment. In situ hybridization demonstrated that Nfil3 mRNA was highly induced in theca-interstitial cells at 4-8 h after hCG, localized to granulosa cells at 12 h, and decreased at 24 h. Overexpression of NFIL3 in granulosa cells inhibited the induction of prostaglandin-endoperoxide synthase 2 (Ptgs2), progesterone receptor (Pgr), epiregulin (Ereg), and amphiregulin (Areg) and down-regulated levels of prostaglandin E2. The inhibitory effect on Ptgs2 induction was reversed by NFIL3 small interfering RNA treatment. In theca-interstitial cells the expression of hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (Hpgd) was also inhibited by NFIL3 overexpression. Data from luciferase assays demonstrated that NFIL3 overexpression decreased the induction of the Ptgs2 and Areg promoter activity. EMSA and chromatin immunoprecipitation analyses indicated that NFIL3 binds to the promoter region containing the DNA-binding sites of cAMP response element binding protein and CCAAT enhancer binding protein-β. In summary, hCG induction of NFIL3 expression may modulate the process of ovulation and theca-interstitial and granulosa cell differentiation by regulating expression of PTGS2, PGR, AREG, EREG, and HPGD, potentially through interactions with cAMP response element binding protein and CCAAT enhancer binding protein-β on their target gene promoters.

Dataset Information

CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1.

Publications

CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1.

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