Differential regulation of mouse germline Ig gamma 1 and epsilon promoters by IL-4 and CD40
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2001-08-01Keywords
Activating Transcription Factor 2Activating Transcription Factors
Animals
Antigens, CD40
B-Lymphocytes
Base Sequence
Basic-Leucine Zipper Transcription Factors
Binding Sites
Blood Proteins
CCAAT-Enhancer-Binding Proteins
Cell Line
Cell Nucleus
Cyclic AMP Response Element-Binding
Protein
DNA-Binding Proteins
G-Box Binding Factors
Gene Expression Regulation
Immunoglobulin epsilon-Chains
Immunoglobulin gamma-Chains
Interleukin-4
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Molecular Sequence Data
NF-kappa B
Promoter Regions (Genetics)
Response Elements
STAT6 Transcription Factor
Signal Transduction
Spleen
Trans-Activation (Genetics)
Trans-Activators
Transcription Factors
Tumor Cells, Cultured
Life Sciences
Medicine and Health Sciences
Women's Studies
Metadata
Show full item recordAbstract
Before Ig class switching, RNA transcription through the specific S regions undergoing recombination is induced by cytokines and other activators that induce and direct switching. The resulting germline (GL) transcripts are essential for switch recombination. To understand the differential regulation of mouse IgG1 and IgE, we compared the promoters for GL gamma1 and epsilon transcripts. We addressed the question of why the promoter that regulates GL epsilon transcription is more responsive to IL-4 than the gamma1 promoter and also why GL epsilon transcription is more dependent on IL-4 than is gamma1 transcription. We found that the IL-4-responsive region of the GL epsilon promoter is more inducible than that of the gamma1 promoter, although each promoter contains a binding site for the IL-4-inducible transcription factor Stat6, located immediately adjacent to a binding site for a basic region leucine zipper (bZip) family protein. However, the arrangement and sequences of the sites differ between the epsilon and gamma1 promoters. The GL epsilon promoter binds Stat6 with a 10-fold higher affinity than does the gamma1 promoter. Furthermore, the bZip elements of the two promoters bind different transcription factors, as the GL epsilon promoter binds and is activated by AP-1, whereas the gamma1 promoter binds and is activated by activating transcription factor 2. C/EBPbeta and C/EBPgamma also bind the gamma1 bZip element, although they inhibit rather than activate transcription. However, inhibition of promoter activity by C/EBPbeta does not require the bZip element and may instead occur via inhibiting the activity of NF-kappaB.Source
J Immunol. 2001 Aug 1;167(3):1522-34.
DOI
10.4049/jimmunol.167.3.1522Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50660PubMed ID
11466373Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.167.3.1522
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