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Originally published In Press as doi:10.1074/jbc.M104681200 on July 25, 2001

J. Biol. Chem., Vol. 276, Issue 39, 36383-36390, September 28, 2001
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Human Sex Hormone-binding Globulin Promoter Activity Is Influenced by a (TAAAA)n Repeat Element within an Alu Sequence*

Kevin N. Hogeveen, Marja Talikka, and Geoffrey L. HammondDagger

From the Departments of Obstetrics & Gynaecology and Pharmacology & Toxicology and the Canadian Institutes of Health Research Group in Fetal and Neonatal Health and Development, University of Western Ontario, London, Ontario N6A 4L6, Canada

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.

* This work was supported by an operating grant (to G. L. H) and a studentship (to K. N. H) from the Canadian Institutes of Health Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: London Regional Cancer Center, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada. Tel.: 519-685-8617; Fax: 519-685-8616; E-mail: ghammond@ uwo.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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