Title: Selective DNA recognition by the androgen receptor as a mechanism for hormone-specific regulation of gene expression
Authors: Verrijdt, Guy ×
Haelens, Anna
Claessens, Frank #
Issue Date: Mar-2003
Series Title: Molecular genetics and metabolism. vol:78 issue:3 pages:175-85
Abstract: The androgen receptor (AR) is a member of the highly conserved group of the class I steroid hormone receptors, a subgroup of the nuclear receptor superfamily of ligand-induced transcription factors. All class I receptors influence the expression of their target genes by binding three-nucleotide spaced partial palindromic repeats of the core 5'-TGTTCT-3' motif. The implication that all class I receptors activate transcription by binding similar DNA motifs, poses the problem of how the in vivo steroid-specificity of transcriptional control is achieved. The AR, however, is able to interact with DNA motifs that are divergent from the classical hormone response elements. We will describe this AR-specific DNA interaction in the context of the general mechanisms that dictate the sequence-specificity of DNA-binding and dimerization of the nuclear receptors. The androgen receptor is the only steroid hormone receptor that is able to interact with response elements that are essentially arranged as a direct repeat of the 5'-TGTTCT-3' monomer binding element. We propose that the DNA-binding domain of the AR can interact with these androgen-specific response elements in a head-to-tail conformation, similar to many other nuclear hormone receptors. The fact that subtle differences in the sequence of response elements can dictate androgen-specific responses is a new and intriguing finding. It creates new possibilities in the research on hormone-selective action and provides a new angle in the search for selective ligands or co-factors that might influence androgen receptor action via either type of DNA motif.
ISSN: 1096-7192
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry Section (Medicine) (-)
Laboratory of Molecular Endocrinology
× corresponding author
# (joint) last author

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