Two Different Transcription Factors Discriminate the −315C>T Polymorphism of theFcεRIα Gene: Binding of Sp1 to −315C and of a High Mobility Group-Related Molecule to −315T

Abstract

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.

Critical Roles for PU.1, GATA1, and GATA2 in the Expression of Human FcεRI on Mast Cells: PU.1 and GATA1 Transactivate FCER1A, and GATA2 Transactivates FCER1A and MS4A2

“…This result indicates that knock- Binding motifs for GATA family and PU.1 in the FCER1A promoter were identified in our previous study (4,5). T allele at the 266 single nucleotide polymorphism site (shown with an asterisk) in the FCER1A gene causes an additional GATA motif resulting in the tandem repeat of GATA motifs (33,34). Quantitative analysis of PU.1 (B, F), GATA1 (C, G), and GATA2 (D, H) binding to FCER1A (B-D) and MS4A2 (F-H).…”

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…98 FceRI regulates the concentration of circulating IgE antibodies; among its genetic variants, the C/T transition at À315 in the promoter of the a-chain gene is related to increased IgE levels. 99 Polymorphisms in these FcaRI and FceRI will probably affect the ability of the already-infected embryo/fetus to respond properly to T. gondii, but little can be suspected about their role in vertical transmission, as they are not present in the syncytiotrophoblast.…”

Fusion of OTT to BSAC Results in Aberrant Up-regulation of Transcriptional Activity

“…Chromatin Immunoprecipitation (ChIP) Assay-The ChIP assay was performed using a ChIP Assay kit (Millipore) as previously described (23). Quantitative PCRs were performed using TaqMan Universal PCR master mix and a 7500 RealTime PCR system (Applied Biosystems).…”