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| Status |
Public on Oct 08, 2015 |
| Title |
Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin conformation amenable to epigenetic manipulation |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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 since it does not eliminate nuclear HBV cccDNA, the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target the transcriptional regulation of cccDNA 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 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 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.
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| Overall design |
Mapping of mutiple histone modifications in HBV cccDNA from infected HepG2 cells, primary hepatocytes and HBV infected liver tissue
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| Contributor(s) |
Tropberger P, Mercier A, Robinson M, Zhong W, Ganem D, Holdorf MM |
| Citation(s) |
26438841 |
| Submission date |
Apr 29, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Philipp Tropberger |
| E-mail(s) |
ptropberger@gmail.com
|
| Organization name |
Novartis Institutes for BioMedical Research
|
| Street address |
4560 Horton Street
|
| City |
Emeryville |
| ZIP/Postal code |
94608 |
| Country |
USA |
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| Platforms (2) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA282651 |
| SRA |
SRP057801 |
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