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Volume 270, Number 18, Issue of May 5, pp. 10733-10742, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.

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Mouse Interleukin-2 Receptor Gene Expression
DELIMITATION OF cis-ACTING REGULATORY ELEMENTS IN TRANSGENIC MICE AND BY MAPPING OF DNase-I HYPERSENSITIVE SITES

Elisabetta Soldaini , Maria Pla , Friedrich Beermann , Enric Espel , Patricia Corthésy , Sonia Barangé , Gary A. Waanders , H. Robson MacDonald , Markus Nabholz

The chain of the interleukin-2 receptor (IL-2R) 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-2R 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-2R gene expression. These results show that regulation of the endogenous IL-2R 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-2R 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.

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