BPTF regulates androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction

BPTF, the scaffolding subunit of the nucleosome remodeling factor (NURF) complex, has been implicated in the progression of several malignancies, but its role in prostate cancer (PCa) remains unclear. Here, we demonstrate that BPTF is upregulated in castration-resistant prostate cancer (CRPC) and promotes disease progression. RNA-seq revealed that BPTF primarily enhances the expression of androgen receptor (AR) target genes. ChIP-seq showed that BPTF increases AR binding at promoters, enhancers and super-enhancers. ATAC-seq further demonstrated that BPTF increases chromatin accessibility to facilitate AR binding, in part through SMARCA1, a catalytic subunit of the NURF complex. Notably, BPTF/AR co-bound regions are highly enriched for FOXA1 motifs but only weakly enriched for AR motifs. We further show that BPTF forms a protein complex with AR and FOXA1, in which FOXA1 recruits the BPTF-AR complex 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, impairs AR signaling and suppresses 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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-12-11
DOI
https://doi.org/10.1038/s41467-025-67329-9
Primary Topic
Protein Degradation and Inhibitors
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

BPTF regulates androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction

Hegang Chen, Hung‐Ming Lam, Eva Corey, Arif Hussain et al.
Nature Communications
Protein Degradation and Inhibitors
article

BPTF regulates androgen receptor activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 interaction

Hegang Chen, Hung‐Ming Lam, Eva Corey, Arif Hussain, Jianfei Qi, Christopher E. Barbieri, Htoo Zarni Oo, Sudeep Khadka, Martin Gleave, Majid Pornour, Xiaofang Che, Heeyoung Jeon, Hyunju Ryu
article en

Abstract

BPTF, the scaffolding subunit of the nucleosome remodeling factor (NURF) complex, has been implicated in the progression of several malignancies, but its role in prostate cancer (PCa) remains unclear. Here, we demonstrate that BPTF is upregulated in castration-resistant prostate cancer (CRPC) and promotes disease progression. RNA-seq revealed that BPTF primarily enhances the expression of androgen receptor (AR) target genes. ChIP-seq showed that BPTF increases AR binding at promoters, enhancers and super-enhancers. ATAC-seq further demonstrated that BPTF increases chromatin accessibility to facilitate AR binding, in part through SMARCA1, a catalytic subunit of the NURF complex. Notably, BPTF/AR co-bound regions are highly enriched for FOXA1 motifs but only weakly enriched for AR motifs. We further show that BPTF forms a protein complex with AR and FOXA1, in which FOXA1 recruits the BPTF-AR complex 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, impairs AR signaling and suppresses 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.

Nature CommunicationsVol. 17(1)
University of Maryland, Baltimore (US), University of British Columbia (CA), University of Washington (US), Cornell University (US), Veterans Health Administration (US), First Hospital of China Medical University (CN), Sidney Kimmel Comprehensive Cancer Center (US), Weill Cornell Medicine (US), University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Baltimore (US), China Medical University (CN)
U.S. Department of Defense, U.S. Department of Veterans Affairs, Prostate Cancer Foundation, National Institutes of Health, National Cancer Institute
Openalex Percentile: Top 64%
Protein Degradation and Inhibitors
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.