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Title: Change of specificity mutations in androgen-selective enhancers. Evidence for a role of differential DNA binding by the androgen receptor
Authors: Verrijdt, Guy ×
Schoenmakers, Erik
Haelens, Anna
Peeters, Benjamin
Verhoeven, Guido
Rombauts, Wilfried
Claessens, Frank #
Issue Date: Apr-2000
Series Title: Journal of Biological Chemistry vol:275 issue:16 pages:12298-305
Abstract: The androgen and glucocorticoid receptors recognize identical DNA motifs, leaving unanswered the question of how steroid specificity of transcriptional regulation is established in cells containing both receptors. Here, we provide evidence that subtle differences in low affinity DNA recognition might be a crucial element in the generation of steroid-specific responses. Here we identify simple hormone response elements in the mouse sex-limited protein enhancer and the human secretory component androgen response unit to be essential for the androgen specificity of both enhancers. We describe specific in vitro binding to these motifs by the DNA-binding domain of the androgen but not the glucocorticoid receptor. Both elements can be considered partial direct repeats of the 5'-TGTTCT-3' core binding motif. In addition, we show that specific point mutations in their left half-sites, essentially changing the nature of the repeats, strongly enhance the glucocorticoid sensitivity of the respective enhancers, whereas they have no effect on their androgen responsiveness. Accordingly, these mutations allow specific binding of the glucocorticoid receptor DNA-binding domain to both elements in vitro. With these experiments, we demonstrate that differential recognition by the androgen receptor of nonconventional steroid response elements is, at least in some cases, an important mechanism in androgen-specific transcriptional regulation.
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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