The androgen and glucocorticoid hormones evoke specific in vivo responses by activating different sets of responsive genes. Although the consensus sequences of the glucocorticoid and androgen response elements are very similar, this in vivo specificity can in some cases be explained by differences in DNA recognition between both receptors. This has clearly been demonstrated for the androgen response element PB-ARE-2 described in the promoter of the rat probasin gene. Swapping of different fragments between the androgen- and glucocorticoid-receptor DNA-binding domains demonstrates that (i) the first Zn-finger module is not involved in this sequence selectivity and (ii) that residues in the second Zn-finger as well as a C-terminal extension of the DNA-binding domain from the androgen receptor are required. For specific and high-affinity binding to response elements, the DNA-binding domains of the androgen and glucocorticoid receptors need a different C-terminal extension. The glucocorticoid receptor requires 12 C-terminal amino acids for high affinity DNA binding, while the androgen receptor only involves four residues. However, for specific recognition of the PB-ARE-2, the androgen receptor also requires 12 C-terminal residues. Our data demonstrate that the mechanism by which the androgen receptor binds selectively to the PB-ARE-2 is different from that used by the glucocorticoid receptor to bind a consensus response element. We would like to suggest that the androgen receptor recognizes response elements as a direct repeat rather than the classical inverted repeat.
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August 1999
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Research Article|
July 26 1999
Differential DNA binding by the androgen and glucocorticoid receptors involves the second Zn-finger and a C-terminal extension of the DNA-binding domains
Erik SCHOENMAKERS;
Erik SCHOENMAKERS
*Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
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Philippe ALEN;
Philippe ALEN
*Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
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Guy VERRIJDT;
Guy VERRIJDT
*Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
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Ben PEETERS;
Ben PEETERS
*Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
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Guido VERHOEVEN;
Guido VERHOEVEN
†Laboratory for Experimental Medicine and Endocrinology, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
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Wilfried ROMBAUTS;
Wilfried ROMBAUTS
*Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
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Frank CLAESSENS
Frank CLAESSENS
1
*Division of Biochemistry, Faculty of Medicine, Campus Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium
1To whom correspondence should be addressed (e-mail frank.claessens@med.kuleuven.ac.be).
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Publisher: Portland Press Ltd
Received:
February 18 1999
Revision Received:
April 12 1999
Accepted:
May 12 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 341 (3): 515–521.
Article history
Received:
February 18 1999
Revision Received:
April 12 1999
Accepted:
May 12 1999
Citation
Erik SCHOENMAKERS, Philippe ALEN, Guy VERRIJDT, Ben PEETERS, Guido VERHOEVEN, Wilfried ROMBAUTS, Frank CLAESSENS; Differential DNA binding by the androgen and glucocorticoid receptors involves the second Zn-finger and a C-terminal extension of the DNA-binding domains. Biochem J 1 August 1999; 341 (3): 515–521. doi: https://doi.org/10.1042/bj3410515
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