Elf-1 contributes to the function of the complex interleukin (IL)-2-responsive enhancer in the mouse IL-2 receptor alpha gene.

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_1366
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Elf-1 contributes to the function of the complex interleukin (IL)-2-responsive enhancer in the mouse IL-2 receptor alpha gene.
Périodique
Journal of Experimental Medicine
Auteur(s)
Serdobova I., Pla M., Reichenbach P., Sperisen P., Ghysdael J., Wilson A., Freeman J., Nabholz M.
ISSN
0022-1007 (Print)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
1997
Volume
185
Numéro
7
Pages
1211-1221
Langue
anglais
Résumé
Lymphocytes regulate their responsiveness to IL-2 through the transcriptional control of the IL-2R alpha gene, which encodes a component of the high affinity IL-2 receptor. In the mouse IL-2R alpha gene this control is exerted via two regulatable elements, a promoter proximal region, and an IL-2-responsive enhancer (IL-2rE) 1.3 kb upstream. In vitro and in vivo functional analysis of the IL-2rE in the rodent thymic lymphoma-derived, CD4- CD8- cell line PC60 demonstrated that three separate elements, sites I, II, and III, were necessary for IL-2 responsiveness; these three sites demonstrate functional cooperation. Site III contains a consensus binding motif for members of the Ets family of transcription factors. Here we demonstrate that Elf-1, an Ets-like protein, binds to site III and participates in IL-2 responsiveness. In vitro site III forms a complex with a protein constitutively present in nuclear extracts from PC60 cells as well as from normal CD4- CD8- thymocytes. We have identified this molecule as Elf-1 according to a number of criteria. The complex possesses an identical electrophoretic mobility to that formed by recombinant Elf-1 protein and is super-shifted by anti-Elf-1 antibodies. Biotinylated IL-2rE probes precipitate Elf-1 from PC60 extracts provided site III is intact and both recombinant and PC60-derived proteins bind with the same relative affinities to different mutants of site III. In addition, by introducing mutations into the core of the site III Ets-like motif and comparing the corresponding effects on the in vitro binding of Elf-1 and the in vivo IL-2rE activity, we provide strong evidence that Elf-1 is directly involved in IL-2 responsiveness. The nature of the functional cooperativity observed between Elf-1 and the factors binding sites I and II remains unresolved; experiments presented here however suggest that this effect may not require direct interactions between the proteins binding these three elements.
Mots-clé
Animals, Base Sequence, Binding Sites, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Enhancer Elements, Genetic, Ephrin-A2, Interleukin-2/pharmacology, Mice, Molecular Sequence Data, Mutation, Nuclear Proteins/metabolism, Protein Binding, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins c-ets, Receptors, Interleukin-2/genetics, T-Lymphocytes/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 12:05
Dernière modification de la notice
20/08/2019 12:41
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