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SRX24965135: GSM8335285: HepAD38, DMSO, Pol2, rep1; Homo sapiens; ChIP-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 85.7M spots, 17.3G bases, 5.3Gb downloads

External Id: GSM8335285_r1
Submitted by: Risca, Laboratory of Genome Architecture and Dynamics, Rockefeller University
Study: A nucleosome switch primes Hepatitis B Virus infection [ChIP-Seq]
show Abstracthide Abstract
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).
Sample: HepAD38, DMSO, Pol2, rep1
SAMN41895329 • SRS21668667 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM8335285
Instrument: Illumina NovaSeq 6000
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: Frozen cell pellets were resuspended in SDS buffer (100mM NaCl, 50mM Tris-HCl pH 8.0, 5mM EDTA, 0.5 % SDS, 1x protease inhibitor cocktail from Roche). The resulting nuclei were spun down, resuspended in the immunoprecipitation buffer at 1mL per 0.5 million cells (SDS buffer and Triton Dilution buffer [100mM NaCl, 100mM Tris-HCl pH 8.0, 5mM EDTA, 5% Triton X-100] mixed in 2:1 ratio with the addition of 1x protease inhibitor cocktail) and processed on a Covaris E220 Focused-ultrasonicator to achieve an average fragment length of 200-300bps with the following parameters: PIP=140, Duty Factor=5, CBP/Burst per sec=200, Time = 1200s. Chromatin concentrations were estimated using the Pierce™ BCA Protein Assay Kit (ThermoFisher Scientific) according to the manufacturer's instructions. The immunoprecipitation reactions were set up in 500uL of the immunoprecipitation buffer in Protein LoBind tubes (Eppendorf) and pre-cleared with 50 µL of Protein G Dynabeads (ThermoFisher Scientific) for two hours at 4 °C. After pre-clearing, the samples were transferred into new Protein LoBind tubes and incubated overnight at 4 °C with the indicated antibodies (Key Resources Table). The next day, 50 µL of BSA-blocked Protein G Dynabeads were added to the reactions and incubated for 2 hours at 4 °C. The beads were then washed two times with low-salt washing buffer (150 mM NaCl, 1 % Triton X-100, 0.1 % SDS, 2 mM EDTA, 20 mM Tris-HCl pH 8.0), two times with high-salt washing buffer (500 mM NaCl, 1 % Triton X-100, 0.1 % SDS, 2 mM EDTA, 20 mM Tris-HCl pH 8.0), two times with LiCL wash buffer (250 mM LiCl, 10 mM Tris-HCl pH 8.0, 1 mM EDTA, 1 % Na-Deoxycholate, 1 % IGEPAL CA-630) and one time with TE buffer (10 mM Tris-HCl pH 8.0, 1 mM EDTA). The samples were then reverse-crosslinked overnight in elution buffer (1 % SDS, 0.1M NaHCO3) and purified using the ChIP DNA Clean & Concentrator kit (Zymo Research) following manufacturer instructions. After quantification of the recovered DNA fragments, libraries were prepared using the ThruPLEX®DNA-Seq kit (Takara) following the manufacturer's instructions, purified with SPRIselect magnetic beads (Beckman Coulter), and quantified using a Qubit Flex fluorometer (ThermoFisher Scientific) and profiled with a TapeStation (Agilent).
Runs: 1 run, 85.7M spots, 17.3G bases, 5.3Gb
Run# of Spots# of BasesSizePublished
SRR2945294185,664,56817.3G5.3Gb2024-06-19

ID:
33301378

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