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Molecular and Cellular Biology, April 1999, p. 2681-2689, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interleukin-2 (IL-2) Regulates the Accessibility of the IL-2-Responsive Enhancer in the IL-2 Receptor alpha  Gene to Transcription Factors

Corinne Rusterholz, Patricia Corthésy Henrioud, and Markus Nabholz*

Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges, Switzerland

Received 19 November 1998/Accepted 20 January 1999

Interleukin-2 (IL-2) responsiveness of T lymphocytes is controlled through transcription of the IL-2 receptor (IL-2R) alpha  subunit by antigen and by IL-2 itself. IL-2 induces IL-2Ralpha transcription via an IL-2-responsive enhancer (IL-2rE), whose activity depends on the cooperative binding of IL-2-induced STAT5 to two sites and of constitutively active Elf-1 to a third one. Here we describe the changes in IL-2rE chromatin that occur in normal T lymphocytes upon activation of IL-2Ralpha expression. In cells induced to transiently express IL-2Ralpha with concanavalin A (which mimics antigen), none of the IL-2rE sites is occupied despite the presence of Elf-1 and STAT1, which bind to the IL-2rE in vitro. The two STAT binding sites are occupied rapidly upon IL-2 stimulation, concomitantly with STAT5 activation. Occupation of the Elf-1 binding site is delayed, although Elf-1 concentration and binding activity are not modified by IL-2. Digestion of T-cell chromatin with DNase I and micrococcal nuclease shows that IL-2 induces the appearance of nuclease-hypersensitive sites flanking the IL-2rE. Thus IL-2, in addition to activating STAT5, appears to regulate IL-2Ralpha transcription by making IL-2Ralpha chromatin accessible to transcription factors.

* Corresponding author. Mailing address: Swiss Institute for Experimental Cancer Research (ISREC), 155 Chemin des Boveresses, CH-1066 Epalinges, Switzerland. Phone: 41 21 692-5834. Fax: 41 21 652-6933. E-mail: Markus.Nabholz{at}isrec.unil.ch.

Molecular and Cellular Biology, April 1999, p. 2681-2689, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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