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

Détails

ID Serval
serval:BIB_236CA505B8AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mouse interleukin-2 receptor alpha gene expression. Delimitation of cis-acting regulatory elements in transgenic mice and by mapping of DNase-I hypersensitive sites.
Périodique
The Journal of biological chemistry
Auteur(s)
Soldaini E., Pla M., Beermann F., Espel E., Corthésy P., Barangé S., Waanders G.A., MacDonald H.R., Nabholz M.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
1995
Peer-reviewed
Oui
Volume
270
Numéro
18
Pages
10733-10742
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, B-Lymphocytes/metabolism, Deoxyribonuclease I/diagnostic use, Gene Expression Regulation, Genes, Lymphocyte Activation, Mice, Mice, Transgenic, Promoter Regions, Genetic, RNA, Messenger/genetics, Receptors, Interleukin-2/genetics, T-Lymphocytes/metabolism, Tissue Distribution
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/02/2010 16:10
Dernière modification de la notice
08/05/2019 15:47
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