Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence.
Sex hormone-binding globulin (SHBG) is the major sex steroid-binding protein in human plasma and is produced by the liver. Plasma SHBG levels vary considerably between individuals and are influenced by hormonal, metabolic, and nutritional factors. We have now found that a (TAAAA)(n) pentanucleotide repeat, located within an alu sequence at the 5' boundary of the human SHBG promoter, influences its transcriptional activity in association with downstream elements, including an SP1-binding site. Furthermore, SHBG alleles within the general population contain at least 6-10 TAAAA repeats, and the transcriptional activity of a human SHBG promoter-luciferase reporter construct containing 6 TAAAA repeats was significantly lower than for similar reporter constructs containing 7-10 TAAAA repeats when tested in human HepG2 hepatoblastoma cells. This difference in transcriptional activity reflected the preferential binding of a 46-kDa liver-enriched nuclear factor to an oligonucleotide containing 6 rather than 7-10 TAAAA repeats. Thus, a (TAAAA)(n) element within the human SHBG promoter influences transcriptional activity in HepG2 cells and may contribute to differences in plasma SHBG levels between individuals.
Hogeveen
K N
KN
Department of Obstetrics & Gynaecology, University of Western Ontario, London, Ontario N6A 4L6, Canada.
Talikka
M
M
Hammond
G L
GL
D000483:Alleles; D020087:Alu Elements; D000818:Animals; D001665:Binding Sites; D015139:Blotting, Southern; D002467:Cell Nucleus / Q000378:metabolism; D018983:DNA Footprinting; D017931:DNA Primers / Q000378:metabolism; D017930:Genes, Reporter; D014644:Genetic Variation; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012738:Sex Hormone-Binding Globulin / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012738:Sex Hormone-Binding Globulin; D008156:Luciferases