GSE125552
Sequence specific suppression of androgen receptor-DNA binding in vivo by a Py-Im polyamide
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. Overall design: ChIP-seq of androgen receptor in 1 prostate cancer cell line with 3 treatments (vehicle, DHT, DHT and Py-Im polyamide)