The human IgE germline promoter is regulated by interleukin-4, interleukin-13, interferon-alpha and interferon-gamma via an interferon-gamma-activated site and its flanking regions.
Class switching to IgE is preceded by the appearance of epsilon germline transcripts, which are induced by interleukin-4 (IL-4) and by IL-13. A 51-bp fragment of the human epsilon germline promoter conferred in reporter gene assays with the erythroleukemic cell line TF-1 upregulation of transcription by IL-4 or IL-13, and repression by interferon-alpha (IFN-alpha) and IFN-gamma. A central IFN-gamma activated sequence within the 51-bp fragment was sufficient for transcriptional regulation by the cytokines in the absence of its normal flanking regions. In contrast, deletion of either upstream or downstream sequences abolished repression by IFN-alpha or INF-gamma, but not upregulation by IL-4 or IL-13. IL-4 stimulated reporter gene transcription required more than ten times higher concentrations than cell proliferation or tyrosine phosphorylation of the IL-4 receptor.
Ezernieks
J
J
Theodor-Boveri-Institut für Biowissenschaften, Universität Würzburg Physiologische Chemie II, Germany.
Schnarr
B
B
Metz
K
K
Duschl
A
A
D000916:Antibody Diversity; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D004742:Enhancer Elements, Genetic; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D015854:Up-Regulation
D016207:Cytokines; D016898:Interferon-alpha; D018793:Interleukin-13; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D004247:DNA