Chromatin remodeler BAF maintains HBV cccDNA transcriptional competence and represents a therapeutic target

Nucleic Acids Research 2026 Open access

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Authors: Dan Huang, Yi Zheng, Enze Deng, Xinlei Ji, Yecheng Zhang, Hao Sun, Yuehua Chen, Yongxuan Yao, Yuan Zhou, Mingxia Zhang, Zhe Zhou, Yinghua Chen
+4 more Dan Su, Xiaoying Fan, XinWen Chen, Rongjuan Pei
DOI: 10.1093/nar/gkag073
Cited by: 2
References: 69

Abstract

Chronic hepatitis B virus (HBV) persistence relies on the chromatin plasticity of covalently closed circular DNA (cccDNA), a viral minichromosome resistant to current therapies. Using proximity labeling (TurboID-dCas9), ChIP-seq and DNA pull-down assays, we identified SMARCC2-a BAF scaffolding subunit-bound to cccDNA enhancer-promoter regions (EnhⅠ/XP, CP/EnhII), where it sustains nucleosome-depleted regions (NDRs) and recruits RNA polymerase II. Genetic or pharmacological BAF inhibition compacted cccDNA chromatin, reduced histone acetylation (AcH3/AcH4), and enhanced SMC5/6-mediated silencing to suppress transcription, with the BAF ATPase inhibitor FHT-2344 reducing serum HBV DNA by 50% (P

Fields of Study & Subjects

Hepatitis B Virus Studies Genomics and Chromatin Dynamics Protein Degradation and Inhibitors

Publication details

Journal / source
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Volume
54
Issue
4
Publication date
23 January 2026
Language
EN