Two Different Transcription Factors Discriminate the −315C>T Polymorphism of the FcεRIα Gene: Binding of Sp1 to −315C and of a High Mobility Group-Related Molecule to −315T
| Autor: | Nobuhiro Nakano, Ko Okumura, Chiharu Nishiyama, Andrzej Szczeklik, Naomi Shimokawa, Tatsuo Fukai, Hideo Yagita, Keiko Maeda, Shunsuke Kanada, Marek Sanak, Hideoki Ogawa, Yusuke Niwa, Daniel P. Potaczek |
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| Rok vydání: | 2008 |
| Předmět: |
Sp1 Transcription Factor
Immunology Single-nucleotide polymorphism Cytosine Nucleotides Biology Polymorphism Single Nucleotide DNA-binding protein Cytosine nucleotide Transcription (biology) Cell Line Tumor Animals Humans Thymine Nucleotides Immunology and Allergy Promoter Regions Genetic Transcription factor Alleles Sp1 transcription factor Receptors IgE Cell Membrane High Mobility Group Proteins Nuclear Proteins hemic and immune systems Molecular biology Basophils Rats DNA-Binding Proteins Minor allele frequency Protein Subunits Chromatin immunoprecipitation Protein Binding Transcription Factors |
| Zdroj: | The Journal of Immunology. 180:8204-8210 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.180.12.8204 |
| Popis: | The α-chain is a specific component of FcεRI, which is essential for the cell surface expression of FcεRI and the binding of IgE. Recently, two single nucleotide polymorphisms (SNPs) in the α-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 α-chain promoter functions, the transcription activity was evaluated by reporter assay. The α-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 FcεRIα 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 FcεRI on basophils was analyzed by flow cytometry, basophils from individuals carrying −315T allele expressed significantly higher amount of FcεRI compared with those of −315C/C. The findings demonstrate that a −315 SNP significantly affects human FcεRI α-chain promoter activity and expression level of FcεRI on basophils by binding different transcription factors to the SNP site. |
| Databáze: | OpenAIRE |
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