title: Transcriptional Downregulation by Nucleotide Substitution with the Minor Allele of rs3760776 Located in the Promoter of FUT6 Gene.
abstract: We examined the promoter activity of an association signal in an upstream region of the gene encoding fucosyltransferae 6 (FUT6) identified from a recent genomewide association study for the N-glycan level. The luciferase assay using reporter constructs with T and C alleles at rs3760776 revealed differential promoter activity. The amount of luciferin expressed with the C allele corresponded to that without the reporter construct (P > 0.05). On the other hand, the expression was dramatically reduced with the T allele (P < 0.05). The difference in transcriptional activity between the two alleles was confirmed by an electrophoretic mobility shift assay. It demonstrated that the promoter with a T allele had a stronger binding affinity to nuclear factors than that with the C allele. We concluded that the T allele of rs3760776 might repress the transcription of the FUT6 gene. Further studies are warranted to understand its underlying mechanism and its influence on susceptibility to potential diseases.
authors.affiliation: School of Systems Biomedical Science, Soongsil University, 511 Sangdo-dong, Dongjak-gu, Seoul, Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Ryoo
authors.forename: Jihye
authors.initials: J
authors.lastname: Ryu
authors.forename: Chaeyoung
authors.initials: C
authors.lastname: Lee
mesh_terms: D000483:Alleles; D015536:Down-Regulation; D005647:Fucosyltransferases / Q000235:genetics*; D006801:Humans; D009711:Nucleotides / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D009711:Nucleotides; D005647:Fucosyltransferases; C515956:FUT6 protein, human