ArticleScientific reports2016
The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Occult hepatitis B virus infection.Nature reviews. Gastroenterology & hepatology · 2026Review
- Insights of HIV-1 and HBV transcriptional regulation by viral transactivator Tat and HBx.Virus genes · 2025Review
- Structural basis of the hepatitis B virus X protein in complex with DDB1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Intrinsically Disordered Region of HBx and Virus-Host Interactions: Uncovering New Therapeutic Approaches for HBV and Cancer.International journal of molecular sciences · 2025Review
- Influence of Occult Hepatitis B Infection on Blood Transfusion Safety and Its Countermeasures.Pathogens (Basel, Switzerland) · 2025Review
- Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.Genes & diseases · 2025Review
- Review
- Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription.Viruses · 2024Review
- Article
- The role of HBV cccDNA in occult hepatitis B virus infection.Molecular and cellular biochemistry · 2023Review
- Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome.Nature communications · 2023Article
- Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions.Biomedicines · 2023Review
- Histone methylation in pre-cancerous liver diseases and hepatocellular carcinoma: recent overview.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Decoding the multifaceted interventions between human sirtuin 2 and dynamic hepatitis B viral proteins to confirm their roles in HBV replication.Frontiers in cellular and infection microbiology · 2023Review
- Canonical and Divergent N-Terminal HBx Isoform Proteins Unveiled: Characteristics and Roles during HBV Replication.Biomedicines · 2021Article
- Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B.World journal of gastroenterology · 2021Review
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- Mechanism and Therapeutic Opportunities of Histone Modifications in Chronic Liver Disease.Frontiers in pharmacology · 2021Review
- KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2021Article
- IFN-α confers epigenetic regulation of HBV cccDNA minichromosome by modulating GCN5-mediated succinylation of histone H3K79 to clear HBV cccDNA.Clinical epigenetics · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients.
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