Mouse interleukin-2 receptor alpha gene expression. Delimitation of cis-acting regulatory elements in transgenic mice and by mapping of DNase-I hypersensitive sites.
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.
Soldaini
E
E
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges, Switzerland.
Pla
M
M
Beermann
F
F
Espel
E
E
Corthésy
P
P
Barangé
S
S
Waanders
G A
GA
MacDonald
H R
HR
Nabholz
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D005796:Genes; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution
D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003850:Deoxyribonuclease I