| First Author | Ligons DL | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 41 | Pages | 34386-99 |
| PubMed ID | 22865857 | Mgi Jnum | J:191591 |
| Mgi Id | MGI:5462142 | Doi | 10.1074/jbc.M112.378687 |
| Citation | Ligons DL, et al. (2012) CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1. J Biol Chem 287(41):34386-99 |
| abstractText | Interleukin-7 receptor alpha (IL-7Ralpha) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Ralpha 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-7Ralpha 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-7Ralpha 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-7Ralpha 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. |
