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Series GSE270130 Query DataSets for GSE270130
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
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.
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).
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
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Submission date Jun 18, 2024
Last update date Jun 21, 2024
Contact name Andres Mansisidor
Organization name Rockefeller University
Department Laboratory of Genome Architecture and Dynamics
Lab Risca
Street address 1230 York Ave Box 176
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (27)
GSM8335283 HepAD38, DMSO, H3k4me3, rep1
GSM8335284 HepAD38, DMSO, H3k4me3, rep2
GSM8335285 HepAD38, DMSO, Pol2, rep1
This SubSeries is part of SuperSeries:
GSE225716 A nucleosome switch primes Hepatitis B Virus infection
BioProject PRJNA1125296

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Supplementary file Size Download File type/resource
GSE270130_RAW.tar 11.7 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA

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