Evidence map›Paper›PMID 27174370›Full record

ArticleScientific reports2016

The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state.

Valentina Alarcon, Sergio Hernández, Lorena Rubio, Francisca Alvarez, Yvo Flores, Manuel Varas-Godoy, Giancarlo V De Ferrari, Michael Kann, Rodrigo A Villanueva, Alejandra Loyola

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 48 citations in OpenAlex.

  1. Occult hepatitis B virus infection.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  2. Review
  3. 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 · 2025
    Article
  4. Review
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  6. Review
  7. Review
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  9. Article
  10. The role of HBV cccDNA in occult hepatitis B virus infection.Molecular and cellular biochemistry · 2023
    Review
  11. Article
  12. Review
  13. 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 · 2023
    Review
  14. Review
  15. Article
  16. Review
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  19. 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 · 2021
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Valentina AlarconFundación Ciencia &Vida, 7780272, Santiago, Chile.
Sergio HernándezLaboratorio de Virus Hepatitis, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
Lorena RubioFundación Ciencia &Vida, 7780272, Santiago, Chile.
Francisca AlvarezFundación Ciencia &Vida, 7780272, Santiago, Chile.
Yvo FloresFundación Ciencia &Vida, 7780272, Santiago, Chile.
Manuel Varas-GodoyCentro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
Giancarlo V De FerrariCentro de Investigaciones Biomédicas. Facultad de Ciencias Biológicas y Facultad de Medicina. Universidad Andres Bello, Santiago, Chile.
Michael KannUniv. de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, Bordeaux, France.
Rodrigo A VillanuevaLaboratorio de Virus Hepatitis, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
Alejandra LoyolaFundación Ciencia &Vida, 7780272, Santiago, Chile.
Fundación Ciencia and Vida · CLUniversidad Andrés Bello · CLCentre National de la Recherche Scientifique · FRSan Sebastián University · CLUniversidad de Los Andes, Chile · CL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AcetylationCell LineChromatinGene Expression Regulation, ViralHepatitis BHepatitis B virusHep G2 CellsHistone DemethylasesHistone-Lysine N-MethyltransferaseHistonesHumansMethylationPromoter Regions, GeneticTrans-ActivatorsViral Regulatory and Accessory ProteinsVirus ReplicationChromatinhepatitis B virus X proteinHistone DemethylasesHistone-Lysine N-MethyltransferaseHistonesKDM1A protein, humanSetd1A protein, humanTrans-ActivatorsViral Regulatory and Accessory Proteins

Identifiers

PMID27174370
PMCPMC4865824
OpenAlexW2363366940

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.