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Updated: Jun 23, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
Functional analysis of -351 interleukin-9 promoter polymorphism reveals an activator controlled by NF-kappaB
S B Early1, P Huyett, K Brown-Steinke
1Asthma and Allergic Diseases Center, Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908-1355, USA.
Abstract:
Genetic studies have shown linkages for asthma to the chromosomal region 5q31-q33 in humans that includes the IL-9 gene. An A-to-G base substitution has been identified at bp -351 in the IL-9 promoter. The role of this polymorphism in IL-9 promoter function was assessed utilizing CD4+ T cells purified from individuals with one or two of the G alleles in comparison to those homozygous for the wild-type A. The presence of an A at -351 (A allele) increased mitogen-stimulated IL-9 transcription twofold in comparison to subjects with one or two G alleles at this position. Binding of nuclear extract proteins from IL-9-producing human cell lines to DNA sequences including this base exchange demonstrated specific binding of the transcription factor NF-kappaB. Binding of NF-kappaB to the IL-9 promoter was confirmed in vivo using the chromatin immunoprecipitation assay. Recombinant NF-kappaB bound to a promoter fragment with the A allele with fivefold higher affinity than it did to a promoter with the G allele. Individuals carrying the A allele of the IL-9 promoter display increased synthesis of IL-9, which may result in strong Th2 immune responses and a modulation of their susceptibility to infectious, neoplastic, parasitic or atopic disease.
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