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| Status |
Public on Jun 19, 2024 |
| Title |
A nucleosome switch primes Hepatitis B Virus infection [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection.
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| Overall design |
We performed RNA-seq and MNase-seq on HEK293T cells that were transfected with hepatitis B virus (HBV) cccDNA over different timepoitns post transfection. We also performed MNase-seq on HBV cccDNA that was reconstituted with nucleosomes at different levels of saturation. Finally, we performed ChIP-seq on cells either constitutively modeling HBV infection (HepAD38) or that were transfected with HBV cccDNA (HepG2).
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| Contributor(s) |
Prescott NA, Mansisidor A, Bram Y, Biaco T, Rendleman J, Faulkner SC, Lemmon AA, Lim C, Hamard P, Koche R, Risca VI, Schwartz RE, David Y |
| Citation missing |
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| Submission date |
Jun 18, 2024 |
| Last update date |
Jun 21, 2024 |
| Contact name |
Andres Mansisidor |
| E-mail(s) |
mansisidor@nyu.edu, mansisidor@rockefeller.edu, amansisi@stevens.edu
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| Organization name |
Rockefeller University
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| Department |
Laboratory of Genome Architecture and Dynamics
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| Lab |
Risca
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| Street address |
1230 York Ave Box 176
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (27)
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| GSM8335286 |
HepAD38, DMSO, Pol2, rep2 |
| GSM8335287 |
HepAD38, DMSO, Input, rep1 |
| GSM8335288 |
HepG2, cccDNA-transfected, DMSO, Input, rep1 |
| GSM8335289 |
HepG2, cccDNA-transfected, DMSO, H2A, rep1 |
| GSM8335290 |
HepG2, cccDNA-transfected, DMSO, H2A, rep2 |
| GSM8335291 |
HepG2, cccDNA-transfected, DMSO, H2B, rep1 |
| GSM8335292 |
HepG2, cccDNA-transfected, DMSO, H2B, rep2 |
| GSM8335293 |
HepG2, cccDNA-transfected, DMSO, H3, rep1 |
| GSM8335294 |
HepG2, cccDNA-transfected, DMSO, H3, rep2 |
| GSM8335295 |
HepG2, cccDNA-transfected, DMSO, H3K4me3, rep1 |
| GSM8335296 |
HepG2, cccDNA-transfected, DMSO, H3K4me3, rep2 |
| GSM8335297 |
HepG2, cccDNA-transfected, DMSO, Pol2, rep1 |
| GSM8335298 |
HepG2, cccDNA-transfected, DMSO, Pol2, rep2 |
| GSM8335299 |
HepG2, cccDNA-transfected, 500nM CBL137, Input, rep1 |
| GSM8335300 |
HepG2, cccDNA-transfected, 500nM CBL137, H2A, rep1 |
| GSM8335301 |
HepG2, cccDNA-transfected, 500nM CBL137, H2A, rep2 |
| GSM8335302 |
HepG2, cccDNA-transfected, 500nM CBL137, H2B, rep1 |
| GSM8335303 |
HepG2, cccDNA-transfected, 500nM CBL137, H2B, rep2 |
| GSM8335304 |
HepG2, cccDNA-transfected, 500nM CBL137, H3, rep1 |
| GSM8335305 |
HepG2, cccDNA-transfected, 500nM CBL137, H3, rep2 |
| GSM8335306 |
HepG2, cccDNA-transfected, 500nM CBL137, H3K4me3, rep1 |
| GSM8335307 |
HepG2, cccDNA-transfected, 500nM CBL137, H3K4me3, rep2 |
| GSM8335308 |
HepG2, cccDNA-transfected, 500nM CBL137, Pol2, rep1 |
| GSM8335309 |
HepG2, cccDNA-transfected, 500nM CBL137, Pol2, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE225716 |
A nucleosome switch primes Hepatitis B Virus infection |
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| Relations |
| BioProject |
PRJNA1125296 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE270130_RAW.tar |
11.7 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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