Mouse interleukin-2 receptor α gene expression: Delimitation of cis-acting regulatory elements in transgenic mice and by mapping of DNase-I hypersensitive sites

The α chain of the interleukin-2 receptor (IL-2Rα) is a key regulator of lymphocyte proliferation. To analyze the mechanisms controlling its expression in normal cells, we used the 5′-flanking region (base pairs -2539/ +93) of the mouse gene to drive chloramphenicol acetyltransferase expression in four transgenic mouse lines. Constitutive transgene activity was restricted to lymphoid organs. In mature T lymphocytes, transgene and endogenous IL-2Rα gene expression was stimulated by concanavalin A and up-regulated by IL-2 with very similar kinetics. In thymic T cell precursors, IL-1 and IL-2 cooperatively induced transgene and IL-2Rα gene expression. These results show that regulation of the endogenous IL-2Rα gene occurs mainly at the transcriptional level. They demonstrate that cis-acting elements in the 5′-flanking region present in the transgene confer correct tissue specificity and inducible expression in mature T cells and their precursors in response to antigen, IL-1, and IL-2. In a complementary approach, we screened the 5′ end of the endogenous IL-2Rα gene for DNase-I hypersensitive sites. We found three lymphocyte specific DNase-I hypersensitive sites. Two, at -0.05 and -5.3 kilobase pairs, are present in resting T cells. A third site appears at -1.35 kilobase pairs in activated T cells. It co-localizes with IL-2-responsive elements identified by transient transfection experiments.