Article: article from journal or magazin.
Interleukin-2 (IL-2) regulates the accessibility of the IL-2-responsive enhancer in the IL-2 receptor alpha gene to transcription factors.
Molecular and Cellular Biology
Publication types: Journal Article
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.
Animals, Concanavalin A/pharmacology, DNA Footprinting, DNA-Binding Proteins/metabolism, Enhancer Elements, Genetic, Gene Expression Regulation, Interleukin-2/pharmacology, Lymphocyte Activation, Mice, Mice, Inbred DBA, Milk Proteins, Nuclear Proteins, Nucleosomes/metabolism, Protein Binding, Receptors, Interleukin-2/biosynthesis, Receptors, Interleukin-2/genetics, Regulatory Sequences, Nucleic Acid, Response Elements, STAT1 Transcription Factor, STAT5 Transcription Factor, Spleen/cytology, T-Lymphocytes/cytology, T-Lymphocytes/metabolism, Trans-Activators/metabolism, Transcription Factors/metabolism
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