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BPTF regulstes androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction [Cut&Run]

GSE287902 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 40 samples Submitted 2025/11/17 Platform GPL24676
Summary
BPTF, the scaffolding subunit of the nucleosome remodeling factor (NURF) complex, has been implicated in the progression of various malignancies. However, its role in prostate cancer (PCa) remains poorly understood. Here, we demonstrate that BPTF is upregulated in castration-resistant prostate cancer (CRPC) and promotes disease progression. RNA-seq revealed that BPTF primarily upregulates the expression of androgen receptor (AR) target genes. ChIP-seq showed that BPTF facilitates AR binding to enhancers and super-enhancers, while ATAC-seq demonstrated that BPTF increases chromatin accessibility to facilitate AR binding, partly via SMARCA1, a catalytic subunit of the NURF complex. Notably, BPTF/AR shared ChIP-seq peaks are highly enriched for FOXA1 motifs but only weakly enriched for AR motifs. We find that BPTF interacts with both FOXA1 and AR to form a protein complex in which FOXA1 recruits BPTF-AR to chromatin, while BPTF stabilizes the AR–FOXA1 interaction. Importantly, BPTF interacts with AR through its bromodomain, and a BPTF bromodomain inhibitor disrupts this interaction, leading to impaired AR signaling and suppressed PCa cell growth. In summary, our findings establish BPTF as a critical regulator of AR activity by promoting chromatin accessibility and stabilizing the AR–FOXA1 complex, highlighting BPTF as a potential therapeutic target in prostate cancer.
Published in
BPTF regulates androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction
Jeon HY, Khadka S, Pornour M et al. · Nature communications 2025 · PMID 41381516 · doi:10.1038/s41467-025-67329-9
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Direct links to NCBI, no account and no request form: the whole study as GSE287902_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 40 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1215252 and SRA study SRP559621. Searching any of these in the dataset finder brings you back here.

Study design
19 conditions, mostly in duplicate
Rv1, control, BPTF, ×2 Rv1, BPTFKD, BPTF, ×2 Rv1, control, AR, ×2 Rv1, BPTFKD, AR, ×2 Rv1, control, FOXA1, ×2 Rv1, BPTFKD, FOXA1, ×2 Rv1, control, BPTF, forARKD, ×2 Rv1, ARKD, BPTF, ×2 +13 more

Supports a between-group comparison across 38 samples.

19 replicated groups read from 40 sample titles; they account for 38 of them. Check it against the sample list below before relying on it.

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