Activation of the mouse Ig germline epsilon promoter by IL-4 is dependent on AP-1 transcription factors
Shen, Ching-Hung ; Stavnezer, Janet
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Authors
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
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
Subject Area
Embargo Expiration Date
Link to Full Text
Abstract
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.
Source
J Immunol. 2001 Jan 1;166(1):411-23. Link to article on publisher's site