       Document 0085
 DOCN  M9640085
 TI    Polymorphic nucleotides within the human IL-4 promoter that mediate
       overexpression of the gene.
 DT    9604
 AU    Song Z; Casolaro V; Chen R; Georas SN; Monos D; Ono SJ; Department of
       Medicine, Johns Hopkins University School of; Medicine, Baltimore, MD
       21224, USA.
 SO    J Immunol. 1996 Jan 15;156(2):424-9. Unique Identifier : AIDSLINE
       MED/96132964
 AB    Atopy, which predisposes individuals to develop asthma, severe systemic
       anaphylaxis, and atopic dermatitis, is usually associated with
       dramatically elevated total serum IgE levels and is thought to be
       controlled by a major susceptibility gene and multiple minor
       susceptibility genes. A recent sib-pair analysis revealed a tight
       linkage between markers on 5q31.1 and a major susceptibility gene
       controlling total serum IgE levels. Due to its location within this
       cluster and its biologic role in Ig class switching and Th2 cell
       differentiation, the IL-4 gene has emerged as one major candidate for
       the atopy gene. In one model, polymorphisms within IL-4 regulatory
       elements might result in overexpression of the gene, amplifying Th2 cell
       differentiation and class switching to IgE. In support of this model, we
       report that the human IL-4 promoter exists in multiple allelic forms
       that exhibit distinct transcriptional activities in IL-4-positive T
       cells. A particular allele has an unusually high transcriptional
       activity. A nucleotide substitution within a recently described OAP40
       element located just upstream of an NF-AT site (P sequence) appears to
       be largely responsible for the increased promotor strength of this
       particular allelic form of the IL-4 promoter. In EMSAs, this
       substitution results in a markedly enhanced affinity for
       sequence-specific complexes exhibiting an AP-1 specificity. The
       identification of allelic nucleotides, which results in overexpression
       of the IL-4 gene, provides specific targets for a comprehensive
       screening of atopic and nonatopic individuals and may provide a clue for
       genetic predisposition for atopy.
 DE    Alleles  B-Lymphocytes  Base Sequence  Cell Line, Transformed
       Comparative Study  Disease Susceptibility/GENETICS/IMMUNOLOGY  *Gene
       Expression Regulation  Human  Hypersensitivity,
       Immediate/*GENETICS/IMMUNOLOGY  IgE/BIOSYNTHESIS
       Interleukin-4/*GENETICS  Leukemia, Basophilic, Acute/PATHOLOGY
       Leukemia, T-Cell, Acute/PATHOLOGY  Molecular Sequence Data  Mutagenesis,
       Site-Directed  Promoter Regions (Genetics)/*GENETICS  Sequence Alignment
       Sequence Homology, Nucleic Acid  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Th2 Cells/SECRETION  Transcription Factor AP-1/METABOLISM
       Transcription, Genetic  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

