Genomics

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Sequence specific suppression of androgen receptor-DNA binding in vivo by a Py-Im polyamide


ABSTRACT: The crucial role of androgen receptor in prostate cancer development is well documented, and its inhibition is a mainstay of prostate cancer treatment. Here we analyze the perturbations to the androgen receptor cistrome caused by a minor groove binding molecule that is designed to target a sequence found in a subset of androgen response elements. We find treatment with this pyrrole-imidazole polyamide exhibits sequence selectively in its repression of androgen receptor 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 ARE half-site bearing single or double mismatches to the Py-Im polyamide binding sequence are not enriched. This study represents an indirect determination of Py-Im polyamide binding preference in vivo using an unbiased approach.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125552 | GEO | 2019/02/22

REPOSITORIES: GEO

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