title: Single nucleotide polymorphisms in the human corticosteroid-binding globulin promoter alter transcriptional activity.
abstract: Corticosteroid-binding globulin (CBG) is a high-affinity plasma protein that transports glucocorticoids and progesterone. Others and we have reported non-synonymous single nucleotide polymorphisms (SNPs) that influence CBG production or steroid-binding activity. However, no promoter polymorphisms affecting the transcription of human CBG gene (Cbg) have been reported. In the present study we investigated function implications of six promoter SNPs, including -26 C/G, -54 C/T, -144 G/C, -161 A/G, -205 C/A, and -443/-444 AG/-, five of which are located within the first 205 base pairs of 5'-flanking region and close to the highly conserved footprinted elements, TATA-box, or CCAAT-box. Luciferase reporter assays demonstrated that basal activity of the promoter carrying -54 T or -161 G was significantly enhanced. The first three polymorphisms, -26 C/G, -54 C/T, and -144 G/C located close to the putative hepatic nuclear factor (HNF) 1 binding elements, altered the transactivation effect of HNF1β. We also found a negative promoter response to dexamethasone-activated glucocorticoid receptor (GR) α, although none of the SNPs affected its transrepression function. Our results suggest that human Cbg -26 C/G, -54 C/T, -144 G/C, and -161 A/G promoter polymorphisms alter transcriptional activity, and further studies are awaited to explore their association with physiological and pathological conditions.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.forename: JingHui
authors.initials: J
authors.lastname: Lei
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.forename: HongMei
authors.initials: H
authors.lastname: Wang
authors.forename: XiaoGuang
authors.initials: X
authors.lastname: Yu
authors.forename: HaiYan
authors.initials: H
authors.lastname: Lin
mesh_terms: D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D056945:Hep G2 Cells; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014156:Transcortin / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D051539:Hepatocyte Nuclear Factor 1-beta; D003907:Dexamethasone; D004247:DNA; D014156:Transcortin