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Molecular Endocrinology Vol. 5, No. 11 1587-1596
doi:10.1210/mend-5-11-1587
Copyright © 1991 by the Endocrine Society.
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Multiple Components of a Complex Androgen-Dependent Enhancer

Adam J. Adler, Arno Scheller, Yetta Hoffman and Diane M. Robins

Department of Human Genetics, University of Michigan Medical School Ann Arbor, Michigan 48109–0618

Address requests for reprints to: Dr. Diane M. Robins, Department of Human Genetics, University of Michigan Medical School, Medical Science II 4708, Ann Arbor, Michigan 48109–0618.

Abstract

Sex-limited protein (Slp) is expressed in adult male mice. A 160-basepair fragment 2 kilobases upstream of the gene serves as an androgen-dependent enhancer of chloramphenicol acetyltransferase expression in transient transfection assays in cells with endogenous or cotransfected androgen receptor. One element that is necessary, but not sufficient, for induction is a consensus glucocorticoid (or hormone. response element (HRE). This element binds to the mouse androgen receptor in vitro, but with apparent weak affinity. Induction by the HRE is greatly augmented by an accessory sequence within the 160 basepairs, suggesting that cooperative interactions confer strong response to androgen. Additional elements within the enhancer modulate induction, positively or negatively, and exhibit cellspecific behavior. Of particular interest are two degenerate HREs that are adjacent to the consensus sequence; they show no independent activity, but are functionally significant in conjunction with other elements. The complexity of this enhancer may reflect biological mechanisms that ensure specificity of hormonal response and allow gene expression to respond to changes in hormone concentration.

FOOTNOTES

This work was supported by NIH Grant GM-31546 (to D.M.R.).

Received for publication July 12, 1991. Revision received August 19, 1991. Accepted for publication August 19, 1991.




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