IP-SNPs-seq links noncoding risk alleles to lineage transcription factor programs in prostate cancer.

ABSTRACT: Most prostate cancer risk variants reside in noncoding DNA, but connecting germline alleles to lineage transcription factor (TF) programs has been challenging. We developed immunoprecipitation-coupled SNPs-seq (IP-SNPs-seq), enabling high-throughput, allele-specific, TF-resolved interrogation of candidate regulatory variants. Screening 903 prostate cancer-associated SNPs with androgen receptor (AR) immunoprecipitation, we identified multiple alleles with biased AR binding and convergent evidence from eQTL and ChIP-seq datasets. Among these, rs7600820 emerged as a functional enhancer variant: the risk G allele conferred stronger reporter activity, heightened AR responsiveness to dihydrotestosterone, and increased ODC1 expression; chromatin profiling and Hi-C revealed an active enhancer loop

SUBMITTER: Xu W 

PROVIDER: S-EPMC12686227 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature