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    Regulation of the promoter for human immunoglobulin gamma3 germ-line transcription and its interaction with the 3'alpha enhancer

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    Authors
    Pan, Q.
    Petit-Frere, C.
    Stavnezer, Janet
    Hammarstrom, L.
    UMass Chan Affiliations
    Department of Molecular Genetics and Microbiology
    Document Type
    Journal Article
    Publication Date
    2000-04-01
    Keywords
    Antigens, CD40
    B-Lymphocytes
    Base Sequence
    CCAAT-Enhancer-Binding Proteins
    DNA
    DNA-Binding Proteins
    Drug Synergism
    Enhancer Elements (Genetics)
    Genes, Immunoglobulin
    Humans
    Immunoglobulin Class Switching
    Immunoglobulin G
    Interleukin-4
    Molecular Sequence Data
    Mutagenesis, Insertional
    NF-kappa B
    Nuclear Proteins
    Phorbol 12,13-Dibutyrate
    Promoter Regions (Genetics)
    RNA, Messenger
    Response Elements
    STAT6 Transcription Factor
    Trans-Activation (Genetics)
    Trans-Activators
    Transcription, Genetic
    Tumor Cells, Cultured
    Life Sciences
    Medicine and Health Sciences
    Women's Studies
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    Link to Full Text
    https://doi.org/10.1002/(SICI)1521-4141(200004)30:4<1019::AID-IMMU1019>3.0.CO;2-W
    Abstract
    The mechanism underlying the differential regulation of switching to human IgG subclasses is still largely unknown. We demonstrate that the region upstream of the initiation sites for gamma3 germ-line (GL) transcripts contains a functional promoter which is synergistically induced by IL-4, antibody to CD40 and phorbol dibutyrate in transient transfection assays in the human DG75 cell line. Linker-scanning mutations identified multiple elements in the 3' half of the evolutionarily conserved sequence that are required for inducibility. Electrophoretic mobility shift assays showed that Stat6 and NF-kappaB p50 / p65 are induced after stimulation, and bind to specific sequence motifs within the promoter. Overexpression of Stat6, NF-kappaB p50 / p65 and C / EBPgamma synergistically induced the GL gamma3 promoter. Insertion of DNA segments from the human 3' IgH regions, which may function as a locus control region for switch recombination, greatly activated the promoter in an orientation-independent manner. Duplication of the enhancer fragments resulted in a further increase of promoter activity. The greater enhancement of the HS1,2 fragment from the 3' alpha1 rather than the alpha2 locus may suggest a mechanistic explanation for the differential expression of various isotypes.
    Source

    Eur J Immunol. 2000 Apr;30(4):1019-29.

    DOI
    10.1002/(SICI)1521-4141(200004)30:4<1019::AID-IMMU1019>3.0.CO;2-W
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50667
    PubMed ID
    10760789
    Related Resources

    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1002/(SICI)1521-4141(200004)30:4<1019::AID-IMMU1019>3.0.CO;2-W
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