Genomics

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Darolutamide antagonizes androgen signaling by blocking enhancer and super-enhancer activation [ChIP-seq]


ABSTRACT: The androgen receptor (AR) antagonist darolutamide has very recently been approved for the treatment of non-metastatic castration resistant prostate cancer (PCa). Here we determined the genome-wide effects of darolutamide on cis-acting regulatory elements involved in androgen signaling with a focus on enhancer and super-enhancer (SE) regions. Darolutamide strongly depleted the AR from regulatory elements and abolished the AR transcriptional signaling. Using two different androgen-dependent PCa cell lines we identified genomic-regions with different affinities for the AR in androgen-stimulated, androgen-depleted and darolutamide-antagonized conditions. Altogether, our findings demonstrate that darolutamide is a potent AR antagonist blocking genome-wide AR signaling and AR enhancer activation. Further, we show a dynamic AR cistrome and concomitant adapting chromatin environment to varying conditions and identified regions with high AR affinity in cell lines and tissue samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148358 | GEO | 2020/04/10

REPOSITORIES: GEO

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