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 C...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 HNF1.We also found a negative promoter response to dexamethasone-activated glucocorticoid receptor(GR),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.展开更多
基金supported by the National Basic Research Program of China (Grant No. 2011CB944403)the Knowledge Innovation Program of Chinese Academy of Sciences (GrantNo. KSCX3-IOZ-1005)
文摘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 HNF1.We also found a negative promoter response to dexamethasone-activated glucocorticoid receptor(GR),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.
