Two different transcription factors discriminate the -315C>T polymorphism of the Fc epsilon RI alpha gene: binding of Sp1 to -315C and of a high mobility group-related molecule to -315T

J Immunol. 2008 Jun 15;180(12):8204-10. doi: 10.4049/jimmunol.180.12.8204.

Abstract

The alpha-chain is a specific component of FcepsilonRI, which is essential for the cell surface expression of FcepsilonRI and the binding of IgE. Recently, two single nucleotide polymorphisms (SNPs) in the alpha-chain promoter, -315C>T and -66T>C, have been shown by statistic studies to associate with allergic diseases. The effect of -66 SNP on GATA-1-mediated promoter activity has been already indicated. In the present study, to investigate roles of the -315 SNP on the alpha-chain promoter functions, the transcription activity was evaluated by reporter assay. The alpha-chain promoter carrying -315T (minor allele) possessed significantly higher transcriptional activity than that of -315C (major allele). EMSA indicated that the transcription factor Sp1, but not Myc-associated zinc finger protein (MAZ), was bound to the -315C allele probe and that a transcription factor belonging to a high mobility group-family bound to the -315T allele probe. The chromatin immunoprecipitation assay suggested that high mobility group 1, 2, and Sp1 bound around -315 of FcepsilonRIalpha genomic DNA in vivo in the human basophil cell line KU812 with -315C/T and in human peripheral blood basophils with -315C/C, respectively. When cell surface expression level of FcepsilonRI on basophils was analyzed by flow cytometry, basophils from individuals carrying -315T allele expressed significantly higher amount of FcepsilonRI compared with those of -315C/C. The findings demonstrate that a -315 SNP significantly affects human FcepsilonRI alpha-chain promoter activity and expression level of FcepsilonRI on basophils by binding different transcription factors to the SNP site.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Basophils / immunology
  • Basophils / metabolism
  • Cell Line, Tumor
  • Cell Membrane / genetics
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytosine Nucleotides / genetics
  • Cytosine Nucleotides / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Polymorphism, Single Nucleotide / immunology*
  • Promoter Regions, Genetic / immunology
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Protein Subunits / biosynthesis
  • Protein Subunits / genetics*
  • Protein Subunits / metabolism*
  • Rats
  • Receptors, IgE / biosynthesis
  • Receptors, IgE / genetics*
  • Receptors, IgE / metabolism*
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Thymine Nucleotides / genetics
  • Thymine Nucleotides / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Cytosine Nucleotides
  • DNA-Binding Proteins
  • FCER1A protein, human
  • High Mobility Group Proteins
  • Nuclear Proteins
  • Protein Subunits
  • Receptors, IgE
  • Sp1 Transcription Factor
  • Thymine Nucleotides
  • Transcription Factors
  • c-MYC-associated zinc finger protein