Sequence specific suppression of androgen receptor-DNA binding in vivo by a Py-Im polyamide.
Nucleic Acids Res
; 47(8): 3828-3835, 2019 05 07.
Article
em En
| MEDLINE
| ID: mdl-30838415
ABSTRACT
The crucial role of androgen receptor (AR) in prostate cancer development is well documented, and its inhibition is a mainstay of prostate cancer treatment. Here, we analyze the perturbations to the AR cistrome caused by a minor groove binding molecule that is designed to target a sequence found in a subset of androgen response elements (ARE). We find treatment with this pyrrole-imidazole (Py-Im) polyamide exhibits sequence selectivity in its repression of AR binding in vivo. Differentially changed loci are enriched for sequences resembling ARE half-sites that match the Py-Im polyamide binding preferences determined in vitro. Comparatively, permutations of the ARE half-site bearing single or double mismatches to the Py-Im polyamide binding sequence are not enriched. This study confirms that the in vivo perturbation pattern caused by a sequence specific polyamide correlates with its in vitro binding preference genome-wide in an unbiased manner.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Pirróis
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Receptores Androgênicos
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Antagonistas de Receptores de Andrógenos
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Imidazóis
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Antineoplásicos
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Nylons
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos