Selective DNA recognition by the androgen receptor as a mechanism for hormone-specific regulation of gene expression.
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.
Verrijdt
Guy
G
Division of Biochemistry, Laboratory of Biochemistry, Catholic University of Leuven, Campus Gasthuisberg O&N, Herestraat 49, B-3000 Leuven, Belgium.
Haelens
Annemie
A
Claessens
Frank
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D011944:Receptors, Androgen; D004247:DNA