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China Life Sci."],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic hepatitis B is perpetuated by the presence of covalently closed circular DNA (cccDNA) from the hepatitis B virus (HBV) in the liver\u2019s hepatocytes. Despite these efforts, the exact mechanisms by which the chromatin structure of cccDNA enables viral persistence remain unclear. This study investigates the vital role of mammalian SWI\/SNF chromatin remodeling complexes in regulating the transcriptional activity of cccDNA. Our research, using pharmacological inhibitors and genetic techniques, identifies BRG1 (\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    ), the central ATPase of the mSWI\/SNF complexes, and BRD9, a non-canonical BAF (ncBAF)-specific subunit, as crucial host factors for HBV replication. The overexpression of\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    enhances viral propagation, whereas its targeted degradation using PROTAC AU15330 or siRNA significantly reduces cccDNA-driven transcription, viral transcripts, and protein levels. Chromatin accessibility assays demonstrate that the depletion of BRG1 (\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    ) compacts the chromatin at critical cccDNA regulatory regions. Mechanistically, the HBV X protein (HBx) interacts with BAF155 and collaborates with transcription factor YY1 to promote the SWI\/SNF complex binding to viral chromatin. Interestingly, inhibiting BRD9, an ncBAF-specific acetyl-lysine reader, similarly disrupts cccDNA transcription, indicating a coordinated function of canonical and non-canonical SWI\/SNF complexes via acetylation-dependent chromatin remodeling. These insights highlight SWI\/SNF complexes as key regulators of viral persistence and suggest targeting these complexes as a potential therapeutic strategy for eradicating cccDNA reservoirs, potentially leading to a functional cure for chronic HBV infection.\n                  <\/jats:p>","DOI":"10.1007\/s11427-025-3154-3","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T04:44:38Z","timestamp":1763959478000},"page":"3486-3494","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The SWI\/SNF complex mediated chromatin remodeling promotes hepatitis B virus cccDNA transcription"],"prefix":"10.1007","volume":"68","author":[{"given":"Xiaoxue","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"3154_CR1","doi-asserted-by":"publisher","first-page":"123428","DOI":"10.1016\/j.ijbiomac.2023.123428","volume":"230","author":"MM Ali","year":"2023","unstructured":"Ali, M.M., Naz, S., Ashraf, S., Knapp, S., and Ul-Haq, Z. (2023). Epigenetic modulation by targeting bromodomain containing protein 9 (BRD9): its therapeutic potential and selective inhibition. Int J Biol Macromol 230, 123428.","journal-title":"Int J Biol Macromol"},{"key":"3154_CR2","doi-asserted-by":"publisher","first-page":"19975","DOI":"10.1073\/pnas.0908365106","volume":"106","author":"L Belloni","year":"2009","unstructured":"Belloni, L., Pollicino, T., De Nicola, F., Guerrieri, F., Raffa, G., Fanciulli, M., Raimondo, G., and Levrero, M. (2009). Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc Natl Acad Sci USA 106, 19975\u201319979.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3154_CR3","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1080\/22221751.2019.1666661","volume":"8","author":"H Chen","year":"2019","unstructured":"Chen, H., Zhang, Y., Ye, S., Wu, Q., Lin, Y., Sheng, K., Chen, W., Lin, X., and Lin, X. (2019). 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