FcepsilonRIalpha gene -18483A>C polymorphism affects transcriptional activity through YY1 binding

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Genetic polymorphisms in the high-affinity IgE receptor alpha-subunit (FcepsilonRIalpha) are associated with allergic disorders.
• While two polymorphisms are functionally characterized, the -18483A>C (rs2494262) variant's effect on FcepsilonRIalpha expression remains unknown.

Purpose of the Study:

• To investigate the functional impact of the FcepsilonRIalpha -18483A>C (rs2494262) genetic variant on gene transcription.
• To determine if this variant influences the binding of transcription factors to the FcepsilonRIalpha distal promoter in monocytes.

Main Methods:

• Reporter gene assays were used to measure transcriptional activity.
• Electrophoretic mobility shift assays (EMSA) were employed to assess transcription factor binding.

Main Results:

• The -18483A>C variant was confirmed to affect the transcriptional activity of the FcepsilonRIalpha distal promoter.
• Preferential binding of the transcription factor YY1 to the -18483C allele was observed.
• This preferential binding resulted in significantly lower transcriptional activity compared to the -18483A allele.

Conclusions:

• The FcepsilonRIalpha -18483A>C (rs2494262) polymorphism influences FcepsilonRIalpha gene expression.
• YY1 transcription factor binding to the -18483C allele reduces promoter activity, providing a potential mechanism linking this genetic variant to allergic diseases.