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Title: Differences in DNA binding characteristics of the androgen and glucocorticoid receptors can determine hormone-specific responses
Authors: Schoenmakers, Erik ×
Verrijdt, Guy
Peeters, Benjamin
Verhoeven, Guido
Rombauts, Wilfried
Claessens, Frank #
Issue Date: May-2000
Series Title: Journal of Biological Chemistry vol:275 issue:16 pages:12290-7
Abstract: The basis for specificity of gene regulation by steroid hormone receptors remains an important problem in the study of steroid hormone action. One possible mechanism for steroid specificity is the difference in DNA binding characteristics of the receptors, although they share a high homology in their DNA-binding domains. Indeed, the androgen-specific expression of, for example, the probasin (PB) gene can be explained by the presence of an androgen response element (ARE) in its promoter (PB-ARE-2), specifically recognized by the androgen and not by the glucocorticoid receptor. Three residues in the DNA-binding domain of the AR were identified as main determinants for its high affinity for the PB-ARE-2. In addition, the direct repeat nature of this ARE seems to prohibit high affinity binding by the glucocorticoid receptor. This is confirmed by the fact that several imperfect direct repeats of the 5'-TGTTCT-3' core recognition sequence are recognized by the androgen receptor and not by the glucocorticoid receptor. Up to now, only differences between the androgen and glucocorticoid receptor in the transcription activation functions were invoked to explain the specificity of their genomic actions. In the present study, we describe the influence of the DNA-binding domain on the specificity of androgen action. The novelty of our working hypothesis resides in the demonstration of the capacity of the AR-DNA-binding domain to recognize elements with a direct repeat structure.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Biochemistry Section (Medicine) (-)
Laboratory of Molecular Endocrinology
× corresponding author
# (joint) last author

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