Activation of the mouse Ig germline epsilon promoter by IL-4 is dependent on AP-1 transcription factors
Department of Molecular Genetics and Microbiology
Adjuvants, Immunologic; Animals; B-Lymphocytes; Base Sequence; CCAAT-Enhancer-Binding Proteins; CD40 Ligand; Cell Line; Cells, Cultured; DNA-Binding Proteins; Gene Expression Regulation; Genes, Reporter; Half-Life; Humans; Immunoglobulin epsilon-Chains; Interleukin-4; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Multigene Family; Plasmids; Promoter Regions (Genetics); Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; STAT6 Transcription Factor; Signal Transduction; Spleen; Trans-Activators; Transcription Factor AP-1; inhibitors; Transfection; Tumor Cells, Cultured
Life Sciences | Medicine and Health Sciences | Women's Studies
Induction of germline (GL) epsilon transcripts, an essential step preceding Ig isotype switching to IgE, requires activation of transcription factors by IL-4 and a B cell activator, e.g., CD40 ligand or LPS. We demonstrate that AP-1 (Fos and Jun), induced transiently by CD40 ligand or LPS, binds a DNA element in the mouse GL epsilon promoter. AP-1 synergizes with Stat6 to activate both the intact GL epsilon promoter and a minimal heterologous promoter driven by the AP-1 and Stat6 sites of the mouse GL epsilon promoter. By contrast, C/EBP beta, which trans-activates the human GL epsilon promoter, inhibits IL-4 induction of the mouse promoter, probably by attenuating the synergistic interaction between AP-1 and Stat6. Furthermore, AP-1 does not trans-activate the human GL epsilon promoter. Thus, induction of GL epsilon transcripts in mice and humans may be regulated differently. In addition, although mouse GL epsilon transcripts have a half-life of approximately 100 min, the RNA level continues to increase for up to 24 h, and the promoter appears to be active for at least 2 days after B cell activation. Altogether, these data suggest that induction of AP-1 activity, although transient, is required for activation of the mouse GL epsilon promoter by IL-4-induced Stat6.
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Citation: J Immunol. 2001 Jan 1;166(1):411-23. Link to article on publisher's site