In-Vivo Regulation of Interleukin-2 Receptor-Alpha Gene-Transcription by the Coordinated Binding of Constitutive and Inducible Factors in Human Primary T-Cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 1995

In-Vivo Regulation of Interleukin-2 Receptor-Alpha Gene-Transcription by the Coordinated Binding of Constitutive and Inducible Factors in Human Primary T-Cells

M. Algarte
  • Fonction : Auteur
P. Lecine
  • Fonction : Auteur
R. Costello
  • Fonction : Auteur
D. Olive

Résumé

IL-2R alpha transcription is developmentally restricted to T cells and physiologically dependent on specific stimuli such as antigen recognition. To analyse the mechanisms used to activate IL-2R alpha transcription as well as those used to block it in non-expressing cells, we determined the protein-DNA interactions at the IL-2R alpha locus in three different cell types using the DMS/LMPCR genomic footprinting method. CD25/IL-2R alpha can be efficiently induced in primary human T cells since similar to 100% express this gene when receiving an appropriate combination of mitogenic stimuli. To understand why IL-2R alpha is not expressed in other haematopoietic cell types, we analysed BJAB B lymphoma cells which do not express the IL-2R alpha gene and contain constitutively active nuclear NF-kappa B. Primary fibroblasts from embryo and adult skin were selected to examine the mechanisms that may be used to keep the IL-2R alpha gene inactive in non-haematopoietic cells. The three main results are: (i) the stable in vivo occupancy of IL-2R alpha kappa B element in resting T cells, most probably by constitutive NF kappa B p50 homodimer that could impair SRF binding to the flanking SRE/CArG box; (ii) its inducible occupancy by NF-kappa B p50-p65 associated with the binding of an SRE/CArG box DNA-binding factor upon mitogenic stimulation; and (iii) a correlation between the precommitment of T cells to activation and the presence of stable preassembled protein-DNA complexes in contrast with the bare IL-2R alpha locus in non-T cells.
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Dates et versions

hal-02193507 , version 1 (24-07-2019)

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  • HAL Id : hal-02193507 , version 1

Citer

M. Algarte, P. Lecine, R. Costello, A. Plet, D. Olive, et al.. In-Vivo Regulation of Interleukin-2 Receptor-Alpha Gene-Transcription by the Coordinated Binding of Constitutive and Inducible Factors in Human Primary T-Cells. EMBO Journal, 1995, 14 (20), pp.5060--5072. ⟨hal-02193507⟩
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