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Molecular and Cellular Biology, July 2001, p. 4515-4527, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4515-4527.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Novel CD28-Responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor alpha -Chain Locus

Jung-Hua Yeh,1 Patrick Lecine,1 Jacques A. Nunes,1 Salvatore Spicuglia,2 Pierre Ferrier,2 Daniel Olive,1 and Jean Imbert1,*

INSERM U119-IFR57, 13009 Marseilles,1 and Centre d'Immunologie CNRS-INSERM-Univ.Med., 13288 Marseille Cedex 09,2 France

Received 20 December 2000/Returned for modification 13 February 2001/Accepted 16 April 2001

The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) critically regulates the T-cell immune response, and the alpha  chain CD25/IL-2Ralpha is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2Ralpha gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Ralpha gene transcription. By DNase I hypersensitivity analysis, we have identified a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb 5' of the IL-2Ralpha gene. PRRIV/CD28rE contains a functional CRE/TRE element required for CD28 signaling. The T-cell-specific, CD28-responsive expression of the IL-2Ralpha gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors.


* Corresponding author. Mailing address: INSERM U119-IFR57, 27 Blvd. Lei Roure, 13009 Marseilles, France. Phone: 33 (0)491 75 84 04. Fax: 33 (0)491 26 03 64. E-mail: imbert{at}marseille.inserm.fr.


Molecular and Cellular Biology, July 2001, p. 4515-4527, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4515-4527.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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