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

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 tha

SUBMITTER: Kurmis AA 

PROVIDER: S-EPMC6486638 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature