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Determinants of DNA sequence specificity of the androgen, progesterone, and glucocorticoid receptors: evidence for differential steroid receptor response elements.
Nelson, C C; Hendy, S C; Shukin, R J; Cheng, H; Bruchovsky, N; Koop, B F; Rennie, P S.
Afiliação
  • Nelson CC; The Prostate Centre, Jack Bell Research Centre, Vancouver, British Columbia, Canada. ccnelson@interchange.ubc.ca
Mol Endocrinol ; 13(12): 2090-107, 1999 Dec.
Article em En | MEDLINE | ID: mdl-10598584
While androgen, progesterone, and glucocorticoid receptors perform distinct physiological functions by regulating unique sets of genes, in vitro they can transactivate a common high-affinity DNA-binding target. Naturally occurring steroid response elements display nucleotide divergence that lowers binding affinity in comparison to the optimal binding element, but enhances receptor-type specificity. We investigated the role of nucleotide deviations within the DNA-binding site for contribution to steroid receptor specificity. We hypothesized that receptor specificity drives the evolution of binding site sequence, rather than strictly receptor-binding affinity. Receptor-selective targets can evolve by some nucleotides selected on the basis of additional bond energy, and others may be selected by differential tolerance to discourage binding from inappropriate receptors. To identify receptor-specific binding sites, we mimicked these dual selection pressures in a receptor-competitive environment in which DNA binding sites for the androgen or progesterone receptors were selected in the presence of the glucocorticoid receptor. These analyses also demonstrated that steroid receptors strongly select nucleotides in the spacer and flanking regions of the half-site and do so in an asymmetric fashion, indicating that steroid receptors interact with DNA in an allosteric manner that affects the transcriptional activation potential.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Receptores Androgênicos / Receptores de Glucocorticoides / Receptores de Progesterona / Elementos de Resposta Limite: Animals / Humans Idioma: En Revista: Mol Endocrinol Assunto da revista: BIOLOGIA MOLECULAR / ENDOCRINOLOGIA Ano de publicação: 1999 Tipo de documento: Article País de afiliação: Canadá
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Receptores Androgênicos / Receptores de Glucocorticoides / Receptores de Progesterona / Elementos de Resposta Limite: Animals / Humans Idioma: En Revista: Mol Endocrinol Assunto da revista: BIOLOGIA MOLECULAR / ENDOCRINOLOGIA Ano de publicação: 1999 Tipo de documento: Article País de afiliação: Canadá