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| Status |
Public on Mar 03, 2023 |
| Title |
A nucleosome switch primes Hepatitis B Virus infection [Mnase-Seq] |
| Organisms |
Homo sapiens; Hepatitis B virus |
| 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 capable of causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent chromosome, cccDNA, consisting of the circular viral genome and host histones. The first viral protein expressed, HBx, induces degradation of a host silencing factor to facilitate infection. However, the relationship between cccDNA’s chromatin and early HBx transcription state remains poorly understood. Using reconstituted viral chromosomes, we found that nucleosomes in cccDNA drive HBx transcription. We corroborated these findings in cells and further showed that chromatin destabilizing drugs inhibit viral transcription and antigen expression in hepatocytes. Our results shed new light on a long-standing paradox and represent a novel therapeutic avenue for the treatment of chronic HBV.
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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.
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| Contributor(s) |
Prescott NA, Mansisidor A, Bram Y, Lemmon AA, Lim C, Risca VI, Schwartz RE, David Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Feb 21, 2023 |
| 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 (2) |
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| Samples (59)
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| GSM7054608 |
MNase-seq, HBV cccDNA, Empty, In vitro Experiment1 |
| GSM7054609 |
MNase-seq,HBV cccDNA loaded with reconstituted nucleosomes, In vitro Experiment1 |
| GSM7054610 |
MNase-seq,HBV dslDNA loaded with reconstituted nucleosomes, In vitro Experiment1 |
| GSM7054611 |
MNase-seq,HBV cccDNA, Empty, In vitro Experiment 2 |
| GSM7054612 |
MNase-seq,HBV cccDNA, undersaturated nucleosomes, In vitro Experiment 2 |
| GSM7054613 |
MNase-seq,HBV cccDNA, intermediate nucleosomes, In vitro Experiment 2 |
| GSM7054614 |
MNase-seq,HBV cccDNA, saturated nucleosomes, In vitro Experiment 2 |
| GSM7054615 |
MNase-seq,HEK293T cells, mock transfection, t0, 0250U |
| GSM7054616 |
MNase-seq,HEK293T cells, mock transfection, t0, 0500U |
| GSM7054617 |
MNase-seq,HEK293T cells, mock transfection, t0, 1000U |
| GSM7054618 |
MNase-seq,HEK293T cells, mock transfection, t0, 2000U |
| GSM7054619 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 0250U |
| GSM7054620 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 0500U |
| GSM7054621 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 1000U |
| GSM7054622 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 2000U |
| GSM7054623 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 0250U |
| GSM7054624 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 0500U |
| GSM7054625 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 1000U |
| GSM7054626 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 2000U |
| GSM7054627 |
MNase-seq, HBV cccDNA, Empty, In vitro Experiment3, Fully digested |
| GSM7054628 |
MNase-seq, HBV cccDNA, Empty, In vitro Experiment3, Over digested |
| GSM7054629 |
MNase-seq, HBV cccDNA, undersaturated nucleosomes, In vitro Experiment3, Fully digested |
| GSM7054630 |
MNase-seq, HBV cccDNA, undersaturated nucleosomes, In vitro Experiment3, Over digested |
| GSM7054631 |
MNase-seq, HBV cccDNA, intermediate nucleosomes, In vitro Experiment3, Fully digested |
| GSM7054632 |
MNase-seq, HBV cccDNA, intermediate nucleosomes, In vitro Experiment3, Over digested |
| GSM7054633 |
MNase-seq, HBV cccDNA, saturated nucleosomes, In vitro Experiment3, Fully digested |
| GSM7054634 |
MNase-seq, HBV cccDNA, saturated nucleosomes, In vitro Experiment3, Over digested |
| GSM8335854 |
MNase-seq, HepG2.2.15 cells, 100U |
| GSM8335855 |
MNase-seq, HepG2.2.15 cells, 250U |
| GSM8335856 |
MNase-seq, HepAD38, DMSO, 125 U, rep 1 |
| GSM8335857 |
MNase-seq, HepAD38, DMSO, 125 U, rep 2 |
| GSM8335858 |
MNase-seq, HepAD38, DMSO, 125 U, rep 3 |
| GSM8335859 |
MNase-seq, HepAD38, DMSO, 1000 U, rep 1 |
| GSM8335860 |
MNase-seq, HepAD38, DMSO, 1000 U, rep 2 |
| GSM8335861 |
MNase-seq, HepAD38, DMSO, 1000 U, rep 3 |
| GSM8335862 |
MNase-seq, HepAD38, 500 nM CBL137, 125 U, rep 1 |
| GSM8335863 |
MNase-seq, HepAD38, 500 nM CBL137, 125 U, rep 2 |
| GSM8335864 |
MNase-seq, HepAD38, 500 nM CBL137, 125 U, rep 3 |
| GSM8335865 |
MNase-seq, HepAD38,500 nM CBL137 1000 U, rep 1 |
| GSM8335866 |
MNase-seq, HepAD38,500 nM CBL137 1000 U, rep 2 |
| GSM8335867 |
MNase-seq, HepAD38,500 nM CBL137 1000 U, rep 3 |
| GSM8335868 |
MNase-seq, HBV dslDNA assembled into chromatin using Nap1, 1-0X rep1 |
| GSM8335869 |
MNase-seq, HBV dslDNA assembled into chromatin using Nap1, 1-2X rep2 |
| GSM8335870 |
MNase-seq, HBV dslDNA assembled into chromatin using Nap1, 1-4X rep3 |
| GSM8335871 |
MNase-seq, HBV dslDNA assembled into chromatin using Nap1+ACF, 1-0X rep1 |
| GSM8335872 |
MNase-seq, HBV dslDNA assembled into chromatin using Nap1+ACF, 1-2X rep2 |
| GSM8335873 |
MNase-seq, HBV dslDNA assembled into chromatin using Nap1+ACF, 1-4X rep3 |
| GSM8335874 |
MNase-seq,HEK293T cells, mock transfection, t0, 0250U, 50C |
| GSM8335875 |
MNase-seq,HEK293T cells, mock transfection, t0, 0500U, 50C |
| GSM8335876 |
MNase-seq,HEK293T cells, mock transfection, t0, 1000U,50 C |
| GSM8335877 |
MNase-seq,HEK293T cells, mock transfection, t0, 2000U, 50C |
| GSM8335878 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 0250U, 50C |
| GSM8335879 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 0500U, 50C |
| GSM8335880 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 1000U, 50C |
| GSM8335881 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t04, 2000U, 50C |
| GSM8335882 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 0250U, 50C |
| GSM8335883 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 0500U, 50C |
| GSM8335884 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 1000U, 50C |
| GSM8335885 |
MNase-seq, HEK293T cells, HBV cccDNA transfection, t24, 2000U, 50C |
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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 |
PRJNA937215 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE225715_RAW.tar |
1.3 Mb |
(http)(custom) |
TAR (of BEDGRAPH, TBI) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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