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.
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.
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Shunsuke
S
Kanada
Nobuhiro
N
Nakano
Daniel P
DP
Potaczek
Keiko
K
Maeda
Naomi
N
Shimokawa
Yusuke
Y
Niwa
Tatsuo
T
Fukai
Marek
M
Sanak
Andrew
A
Szczeklik
Hideo
H
Yagita
Ko
K
Okumura
Hideoki
H
Ogawa
Chiharu
C
Nishiyama
D000483:Alleles; D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003597:Cytosine Nucleotides / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013942:Thymine Nucleotides / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D003597:Cytosine Nucleotides; D004268:DNA-Binding Proteins; C475664:FCER1A protein, human; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D017455:Receptors, IgE; D016329:Sp1 Transcription Factor; D013942:Thymine Nucleotides; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein