Abstract
Three frequent genetic polymorphisms in the human high-affinity IgE receptor α-subunit (FcεRIα) were shown to be associated with allergic disorders and/or total serum IgE levels in allergic patients. Two of these were previously demonstrated to affect FcεRIα expression while the third –18483A>C (rs2494262) has not yet been subjected to functional studies. We hypothesized that the –18483A>C variant affects transcriptional activity of the FcεRIα distal promoter in monocytes in which FcεRIα transcription is driven through that regulatory region. Indeed, we confirmed preferential binding of the YY1 transcription factor to the –18483C allele, resulting in lower transcriptional activity when compared with the –18483A allele.
This is a preview of subscription content, log in via an institution to check access.
References
Bae JS, Kim SH, Ye YM et al (2007) Significant association of FcεRIα promoter polymorphisms with aspirin-intolerant chronic urticaria. J Allergy Clin Immunol 119:449–456
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265
Griffioen M, Ouwerkerk IJ, Harten V, Schrier PI (2000) HLA-B locus-specific downregulation in human melanoma requires enhancer A as well as a sequence element located downstream of the transcription initiation site. Immunogenetics 52:121–128
Guo J, Casolaro V, Seto E et al (2001) Yin-Yang 1 activates interleukin-4 gene expression in T cells. J Biol Chem 276:48871–48878
Hasegawa M, Nishiyama C, Nishiyama M et al (2003a) Regulation of the human FcεRI α-chain distal promoter. J Immunol 170:3732–3738
Hasegawa M, Nishiyama C, Nishiyama M et al (2003b) A novel -66 T/C polymorphism in FcεRI α-chain promoter affecting the transcription activity: possible relationship to allergic diseases. J Immunol 171:1927–1933
Javahery R, Khachi A, Lo K, Zenzie-Gregory B, Smale ST (1994) DNA sequence requirements for transcriptional initiator activity in mammalian cells. Mol Cell Biol 14:116–127
Kanada S, Nakano N, Potaczek DP et al (2008) Two different transcription factors discriminate the -315C>T-polymorphism of the FcεRI α-chain gene: binding of Sp1 to -315C and of a high mobility group-related molecule to -315 T. J Immunol 180:8204–8210
Maeda K, Nishiyama C, Tokura T et al (2006) FOG-1 represses GATA-1-dependent FcepsilonRI beta-chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice. Blood 108:262–269
Mordvinov VA, Schwenger GT, Fournier R et al (1999) Binding of YY1 and Oct1 to a novel element that downregulates expression of IL-5 in human T cells. J Allergy Clin Immunol 103:1125–1135
Nishiyama C, Hasegawa M, Nishiyama M et al (2001) Cloning of full-length genomic DNA encoding human FcεRI α-chain and its transcriptional regulation. Biochem Biophys Res Commun 284:1056–1064
Nishiyama C, Hasegawa M, Nishiyama M et al (2002) Regulation of human FcεRI α-chain gene expression by multiple transcription factors. J Immunol 168:4546–4552
Nishiyama C, Akizawa Y, Nishiyama M et al (2004) Polymorphisms in the FcεRIβ promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between FcεRIβ and atopy. J Immunol 173:6458–6464
Potaczek DP, Sanak M, Mastalerz L et al (2006) The α-chain of high-affinity receptor for IgE (FcεRIα) gene polymorphisms and serum IgE levels. Allergy 61:1230–1233
Potaczek DP, Sanak M, Mastalerz L, Milewski M, Gawlewicz-Mroczka A, Szczeklik A (2007a) Genetic polymorphisms of the novel FCER1A gene region: relation to total serum IgE levels. Ann Allergy Asthma Immunol 98:500–501
Potaczek DP, Sanak M, Szczeklik A (2007b) Additive association between FCER1A and FCER1B genetic polymorphisms and total serum IgE levels. Allergy 62:1095–1096
Potaczek DP, Nishiyama C, Sanak M, Szczeklik A, Okumura K, Ogawa H (2008) FCER1A gene exon 1A polymorphisms in Japanese and Polish subjects—a comparative analysis of haplotypes. Allergy 63:626–627
Shikanai T, Silverman ES, Morse BW, Lilly CM, Inoue H, Drazen JM (2002) Sequence variants in the FcεRI alpha chain gene. J Appl Physiol 93:37–41
Shrivastava A, Calame K (1994) An analysis of genes regulated by the multi-functional transcriptional regulator Yin Yang-1. Nucleic Acids Res 22:5151–5155
Silverman ES, Palmer LJ, Subramaniam V et al (2004) Transforming growth factor-β1 promoter polymorphism C–509 T is associated with asthma. Am J Respir Crit Care Med 169:214–219
Tregouet DA, Garelle V (2007) A new JAVA interface implementation of THESIAS: testing haplotypes effects in association studies. Bioinformatics 23:1038–1039
Wang QH, Nishiyama C, Nakano N et al (2008) Suppresive effect of Elf-1 on FcεRI α-chain expression in primary mast cells. Immunogenetics 60:557–563
Zhang M, Murphy RF, Agrawal DK (2007) Decoding IgE Fc receptors. Immunol Res 37:1–16
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by a research grant from the Japan Society for the Promotion of Science (JSPS)
Supported by a grant-in-aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan
Electronic supplementary materials
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Potaczek, D.P., Maeda, K., Wang, QH. et al. FcεRIα gene –18483A>C polymorphism affects transcriptional activity through YY1 binding. Immunogenetics 61, 649–655 (2009). https://doi.org/10.1007/s00251-009-0391-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-009-0391-x