CRISPR screening identifies regulators of enhancer-mediated androgen receptor transcription in advanced prostate cancer.

ABSTRACT: Amplification of the androgen receptor (AR) locus is the most frequent alteration in metastatic castration-resistant prostate cancer (CRPC). Recently, it was discovered that an enhancer of the AR is co-amplified with the AR gene body and contributes to increased AR transcription and resistance to androgen deprivation therapy. However, the mechanism of enhancer activation in advanced disease is unknown. Here, we used CRISPR-Cas9 screening to identify transcription factors that bind to the AR enhancer and modulate enhancer-mediated AR transcription. We demonstrate that HOXB13, GATA2, and TFAP2C bind the AR enhancer in patient-derived xenografts and directly impact features associated with an active chromatin state. Interestingly, the AR enhancer belongs to a set of regulatory elements that r

SUBMITTER: Xiang RR 

PROVIDER: S-EPMC11867844 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature