First Author | Yui MA | Year | 2001 |
Journal | J Immunol | Volume | 166 |
Issue | 3 | Pages | 1730-9 |
PubMed ID | 11160218 | Mgi Jnum | J:143704 |
Mgi Id | MGI:3828846 | Doi | 10.4049/jimmunol.166.3.1730 |
Citation | Yui MA, et al. (2001) A new regulatory region of the IL-2 locus that confers position-independent transgene expression. J Immunol 166(3):1730-9 |
abstractText | Although the promoter/enhancer of the IL-2 gene mediates inducible reporter gene expression in vitro, it cannot drive consistent expression in transgenic mice. The location and existence of any regulatory elements that could open the IL-2 locus in vivo have remained unknown, preventing analysis of IL-2 regulation in developmental contexts. In this study, we report the identification of such a regulatory region, marked by novel DNase-hypersensitive sites upstream of the murine IL-2 promoter in unstimulated and stimulated T cells. Inclusion of most of these sites in an 8.4-kb IL-2 promoter green fluorescent protein transgene gives locus control region-like activity. Expression is efficient, tissue specific, and position independent. This transgene is expressed not only in peripheral T cells, but also in immature thymocytes and thymocytes undergoing positive selection, in agreement with endogenous IL-2 expression. In contrast, a 2-kb promoter green fluorescent protein transgene, lacking the new hypersensitive sites, is expressed in only a few founder lines, and expression is dysregulated in CD8(+) cells. Thus, the 6.4 kb of additional upstream IL-2 sequence contains regulatory elements that provide integration site independence and differential regulation of transgene expression in CD8 vs CD4 cells. |