BPTF regulates androgen receptor activity in prostate cancer
Presenter: Jianfei Qi, PhD Session: Chromatin Architecture and Regulatory Landscapes Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Hee-Young Jeon 1 , Sudeep Khadka 1 , Majid Pornour 1 , Hyunju Ryu 1 , Hegang Chen 1 , Arif Hussain 1 , Hung-Ming Lam 2 , Eva Corey 3 , Htoo Zarni Oo 4 , Martin E. Gleave 5 , Xiaofang Che 6 , Christopher E. Barbieri 7 , Jianfei Qi 1 1 University of Maryland School of Medicine, Baltimore, MD, 2 University of Washington Medical Center, Seattle, WA, 3 University of Washington, Seattle, WA, 4 Department of Urologic Sciences, Vancouver Prostate Centre, BC Cancer Agency Vancouver Center, Vancouver, BC, Canada, 5 Distinguised Professor, Dept. of Urological Sciences, University of British Columbia, Vancouver, BC, Canada, 6 Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China, 7 Resident, Weill Cornell Medical College, New York, NY
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 show that BPTF is upregulated in aggressive PCa and promotes disease progression. BPTF knockdown inhibits PCa cell proliferation, while CRISPRa-mediated upregulation promotes androgen-independent growth. To investigate BPTF function, we performed RNA-seq, ChIP-seq and ATAC-seq analyses in BPTF-knockdown PCa cells. RNA-seq analysis reveals that BPTF primarily upregulates androgen receptor (AR) target gene expression. ChIP-seq data show that BPTF facilitates AR binding to enhancers, super-enhancers as well as promoters. ATAC-seq data indicates that BPTF enhances chromatin accessibility at AR-binding sites, partly via SMARCA1, a catalytic subunit of the NURF complex. Notably, BPTF ChIP-seq peaks exhibit strong enrichment of FOXA1 motifs but weak enrichment of AR motifs. We find that BPTF interacts with both FOXA1 and AR to form a protein complex in which FOXA1 anchors BPTF-AR to chromatin, while BPTF stabilizes the AR-FOXA1 interaction. Importantly, BPTF interacts with AR through its bromodomain, and a bromodomain inhibitor disrupts this interaction, leading to impaired AR signaling and suppressed PCa cell growth. In summary, our findings establish BPTF as a key regulator of AR activity by enhancing chromatin accessibility and stabilizing the AR-FOXA1 complex, highlighting BPTF as a potential therapeutic target for prostate cancer.
Disclosure
X. Che, None.. J. Qi, None.
Cited in
Control: 6751 · Presentation Id: 3853 · Meeting 21436