Evidence map›Paper›PMID 26438841›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation.

Philipp Tropberger, Alexandre Mercier, Margaret Robinson, Weidong Zhong, Don E Ganem, Meghan Holdorf

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed
13.5field-weighted citation impact, top 1% 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

142 citing papers in PubMed, 238 citations in OpenAlex.

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  16. 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
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82 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Philipp TropbergerDepartment of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608 don.ganem@novartis.com philipp.tropberger@novartis.com.
Alexandre MercierDepartment of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608.
Margaret RobinsonDepartment of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608.
Weidong ZhongDepartment of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608.
Don E GanemDepartment of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608 don.ganem@novartis.com philipp.tropberger@novartis.com.
Meghan HoldorfDepartment of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608.
Novartis (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection.

Indexed as

Epigenesis, GeneticChromatinDNA, ViralHepatitis B virusHep G2 CellsHistonesHumansPlasmidsTranscription, GeneticChromatinDNA, ViralHistonescccDNAchromatinepigeneticsHBVhepatitis B virus

Identifiers

PMID26438841
PMCPMC4620859
OpenAlexW1906916220

What OpenQuestion holds

Textmetadata
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.