Polymorphisms in the FcεRIβ Promoter Region Affecting Transcription Activity: A Possible Promoter-Dependent Mechanism for Association between FcεRIβ and Atopy

Abstract

The β subunit of the high-affinity IgE receptor (FcεRI) plays an important role in IgE-mediated allergic reactions as an amplifier for cell surface expression and signal transduction of FcεRI. FcεRIβ 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 FcεRIβ and atopic diseases is questionable. In the present study, we found correlation between the SNP of FcεRIβ at +6960A/G, resulting in a Glu237Gly amino acid substitution, and the cell surface expression level of FcεRI on blood basophils, although it has been shown that the Glu237Gly mutation itself does not affect the surface expression or function of FcεRI. We additionally found four SNPs in the promoter region of FcεRIβ, 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 FcεRI β-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 FcεRIβ promoter are causally linked with atopy via regulation of FcεRI expression.

The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

“…A more recent study showed that FcR ␤T isoform competed with the wild-type FcR ␤-subunit during Fc⑀RI assembly in the endoplasmic reticulum preventing proper folding of Fc⑀RI ␣-chain, and it seemed that cotranslational endoplasmic reticulum assembly of Fc⑀RI controlled the formation of a functional IgE-binding Fc⑀RI (27). A subsequent report has also described two single nucleotide polymorphism mutations in potential transcription binding sites of FcR ␤ promoter region that enhanced its gene expression (80). Collectively, these data provide a potential connection between FcR ␤ polymorphisms, Fc⑀RI expression, and atopy.…”

The Transcription Factor Ehf Is Involved in TGF-β–Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells

“…We previously demonstrated that the transcription of genes encoding FcεRIa and FcεRIb is positively regulated by the transcription factors PU.1, GATA-1, and GATA-2 in mast cells (3,5,7,(38)(39)(40)(41). Additionally, GATA-2 also plays an important role in the transcription of the Kit gene (11).…”

Mast Cells Acquire Monocyte-Specific Gene Expression and Monocyte-Like Morphology by Overproduction of PU.1

“…For sorting of c-kitpositive or c-kit/Fc⑀RI-double-positive cells, BD FACSAria Cell Sorter (BD Biosciences, San Jose, CA) was used. Cells stained with each Ab, as described previously (23,24), were analyzed by FACSCalibur flow cytometer (BD Biosciences).…”