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

• Published in: The Journal of biological chemistry Vol. 270; no. 18; pp. 10733 - 10742
• Main Authors: Soldaini, E, Pla, M, Beermann, F, Espel, E, Corthésy, P, Barangé, S, Waanders, G A, MacDonald, H R, Nabholz, M
• Format: Journal Article
• Language: English
• Published: United States 05-05-1995
• Subjects: Animals; B-Lymphocytes - metabolism; Deoxyribonuclease I; Gene Expression Regulation; Genes; Lymphocyte Activation; Mice; Mice, Transgenic; Promoter Regions, Genetic; Receptors, Interleukin-2 - genetics; RNA, Messenger - genetics; T-Lymphocytes - metabolism; Tissue Distribution
• ISSN: 0021-9258
• DOI: 10.1074/jbc.270.18.10733

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