ArticleClinical epigenetics2020
IFN-α confers epigenetic regulation of HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA.
Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Chromatin Accessibility-Guided Targeting Identifies Structurally Constrained Regions in HBV cccDNA and Suppresses Viral Replication.International journal of molecular sciences · 2026Article
- Streptococcus suis disrupts the blood-brain barrier through inducing ubiquitin-proteasome-mediated degradation of KAT2A.Veterinary research · 2026Article
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- The function and mechanism of protein acylation in the regulation of viral infection.Virulence · 2025Review
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Novel histone modifications and liver cancer: emerging frontiers in epigenetic regulation.Clinical epigenetics · 2025Review
- The role of myocardial energy metabolism perturbations in diabetic cardiomyopathy: from the perspective of novel protein post-translational modifications.Clinical epigenetics · 2025Review
- Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.Genes & diseases · 2025Review
- Genome-Wide Association Study to Identify Genetic Factors Linked to HBV Reactivation Following Liver Transplantation in HBV-Infected Patients.International journal of molecular sciences · 2024Article
- Epigenetic modification of hepatitis B virus infection and related hepatocellular carcinoma.Virulence · 2024Review
- The impact of hepatitis B surface antigen seroconversion on the durability of functional cure induced by pegylated interferon alpha treatment.Virology journal · 2024Article
- Article
- Review
- Protein succinylation, hepatic metabolism, and liver diseases.World journal of hepatology · 2024Review
- TNF-α-Induced KAT2A Impedes BMMSC Quiescence by Mediating Succinylation of the Mitophagy-Related Protein VCP.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Protein succinylation: regulating metabolism and beyond.Frontiers in nutrition · 2024Review
- Dysregulation of protein succinylation and disease development.Frontiers in molecular biosciences · 2024Review
- Review
- Unveiling the role of GAS41 in cancer progression.Cancer cell international · 2023Review
- The role of HBV cccDNA in occult hepatitis B virus infection.Molecular and cellular biochemistry · 2023Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis B virus covalently closed circular DNA (HBV cccDNA) is assembled by histones and non-histones into a chromatin-like cccDNA minichromosome in the nucleus. The cellular histone acetyltransferase GCN5, displaying succinyltransferase activity, is recruited onto cccDNA to modulate HBV transcription in cells. Clinically, IFN-α is able to repress cccDNA. However, the underlying mechanism of IFN-α in the depression of cccDNA mediated by GCN5 is poorly understood. Here, we explored the effect of IFN-α on GCN5-mediated succinylation in the epigenetic regulation of HBV cccDNA minichromosome.
resultsSuccinylation modification of the cccDNA minichromosome has been observed in HBV-infected human liver-chimeric mice and HBV-expressing cell lines. Moreover, histone H3K79 succinylation by GCN5 was identified in the system. Interestingly, the mutant of histone H3K79 efficiently blocked the replication of HBV, and interference with GCN5 resulted in decreased levels of HBV DNA, HBsAg, and HBeAg in the supernatant from de novo HBV-infected HepaRG cells. Consistently, the levels of histone H3K79 succinylation were significantly elevated in the livers of HBV-infected human liver-chimeric mice. The knockdown or overexpression of GCN5 or the mutant of GCN5 could affect the binding of GCN5 to cccDNA or H3K79 succinylation, leading to a change in cccDNA transcription activity. In addition, Southern blot analysis validated that siGCN5 decreased the levels of cccDNA in the cells, suggesting that GCN5-mediated succinylation of histone H3K79 contributes to the epigenetic regulation of cccDNA minichromosome. Strikingly, IFN-α effectively depressed histone H3K79 succinylation in HBV cccDNA minichromosome in de novo HepG2-NTCP and HBV-infected HepaRG cells.
conclusionsIFN-α epigenetically regulates the HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA. Our findings provide new insights into the mechanism by which IFN-α modulate the epigenetic regulation of HBV cccDNA minichromosome.
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