دورية أكاديمية
A nucleosome switch primes Hepatitis B Virus infection.
| العنوان: | A nucleosome switch primes Hepatitis B Virus infection. |
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| المؤلفون: | Prescott NA; Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Mansisidor A; Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA.; These authors contributed equally., Bram Y; Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA.; These authors contributed equally., Biaco T; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medicine; New York, NY 10065, USA.; These authors contributed equally., Rendleman J; Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA., Faulkner SC; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Lemmon AA; Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Lim C; Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA., Hamard PJ; Epigenetics Research Innovation Lab, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Koche RP; Epigenetics Research Innovation Lab, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Risca VI; Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA., Schwartz RE; Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine; New York, NY 10065, USA., David Y; Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medicine; New York, NY 10065, USA.; Lead Contact. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 12. Date of Electronic Publication: 2024 Jun 12. |
| نوع المنشور: | Journal Article; Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection. Competing Interests: Declaration of interests R.E.S. is on the scientific advisory boards of Miromatrix Inc. and Lime Therapeutics and is a speaker and consultant for Alnylam Inc. All other authors declare that they have no competing interests. |
| معلومات مُعتمدة: | T32 GM136640 United States GM NIGMS NIH HHS; T32 GM115327 United States GM NIGMS NIH HHS; DP2 GM150021 United States GM NIGMS NIH HHS; P30 CA008748 United States CA NCI NIH HHS; F32 GM140551 United States GM NIGMS NIH HHS; R01 DK121072 United States DK NIDDK NIH HHS; R01 AA027327 United States AA NIAAA NIH HHS; F99 CA264420 United States CA NCI NIH HHS; R01 AI107301 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Hepatitis B Virus; chromatin; epigenetics; nucleosome stability; transcription |
| تواريخ الأحداث: | Date Created: 20240625 Latest Revision: 20240708 |
| رمز التحديث: | 20240708 |
| مُعرف محوري في PubMed: | PMC11195122 |
| DOI: | 10.1101/2023.03.03.531011 |
| PMID: | 38915612 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2692-8205 |
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| DOI: | 10.1101/2023.03.03.531011 |