title: Polymorphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy.
abstract: The beta subunit of the high-affinity IgE receptor (FcepsilonRI) plays an important role in IgE-mediated allergic reactions as an amplifier for cell surface expression and signal transduction of FcepsilonRI. FcepsilonRIbeta is presumed to be one of the genes linked with atopic diseases. However, the validity of the associations previously found between single nucleotide polymorphisms (SNPs) in FcepsilonRIbeta and atopic diseases is questionable. In the present study, we found correlation between the SNP of FcepsilonRIbeta at +6960A/G, resulting in a Glu237Gly amino acid substitution, and the cell surface expression level of FcepsilonRI on blood basophils, although it has been shown that the Glu237Gly mutation itself does not affect the surface expression or function of FcepsilonRI. We additionally found four SNPs in the promoter region of FcepsilonRIbeta, among which -426T/C and -654C/T were tightly linked with +6960A/G. Reporter plasmids carrying the -426C and -654T promoter displayed higher transcriptional activity than those carrying the -426T and -654C promoter. We found that transcription factor YY1 preferentially bound and transactivated the -654T promoter. Furthermore, expression of FcepsilonRI beta-chain mRNA in basophils from individuals who have the minor heterozygous genotype was significantly higher than that of the major homozygous genotype. These results suggest that the SNPs in the FcepsilonRIbeta promoter are causally linked with atopy via regulation of FcepsilonRI expression.
authors.affiliation: Atopy (Allergy) Research Center, Department of Dermatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. chinishi@med.juntendo.ac.jp
authors.forename: Chiharu
authors.initials: C
authors.lastname: Nishiyama
authors.forename: Yushiro
authors.initials: Y
authors.lastname: Akizawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.forename: Kouichi
authors.initials: K
authors.lastname: Mitsuishi
authors.forename: Masanari
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Ito
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takagi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003596:Cytosine; D004268:DNA-Binding Proteins / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D008040:Genetic Linkage; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D021122:Protein Subunits / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D013941:Thymine; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D050986:YY1 Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D021122:Protein Subunits; D017455:Receptors, IgE; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D018698:Glutamic Acid; D003596:Cytosine; D013941:Thymine; D005998:Glycine