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Publication : A new regulatory region of the IL-2 locus that confers position-independent transgene expression.

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.
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