Allergy-associated I epsilon and Ec epsilon receptor II (CD23b) genes activated via binding of an interleukin-4-induced transcription factor to a novel responsive element.
Interleukin-4 (IL-4) has important regulatory functions in the immune system, particularly in the generation of immunoglobulin E, the principal mediator of allergic responses. The molecular basis of IL-4 action has remained elusive so far. Here we report on a novel human transcription factor, termed nuclear factor IL-4 (NF-IL4), which is posttranslationally activated by IL-4 in lymphoid and monocytic cells. Homologous binding sequences for NF-IL4 were identified in the promoter regions of the IL-4 controlled CD23b and I epsilon genes. We defined a palindromic 9-bp consensus sequence (5'-TYCYRRGAA-3') as IL-4-responsive element (IL-4RE). Point mutation analysis of the CD23b promoter showed that binding of NF-IL4 to the IL-4RE is essential for the initiation of gene transcription in response to IL-4. NF-IL4 was not activated by Ca2+ ionophore, phorbol ester and cAMP either alone or in combination suggesting a non classical pathway for IL-4 signal transduction.
Köhler
I
I
Institute for Immunology, University of Munich, FRG.
Rieber
E P
EP
D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017455:Receptors, IgE / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C087516:NF-IL4 protein, human; D017455:Receptors, IgE; D014157:Transcription Factors; D015847:Interleukin-4; D007073:Immunoglobulin E; D013755:Tetradecanoylphorbol Acetate