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| Status |
Public on Jun 27, 2018 |
| Title |
PARP1 Stabilizes CTCF Binding and Chromatin Structure to Maintain Epstein Barr Virus Latency Type |
| Organism |
human gammaherpesvirus 4 |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epstein Barr Virus (EBV) is a potentially oncogenic gammaherpesvirus that establishes a chronic, latent infection in memory B cells. The EBV genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type. CTCF is post-translationally modified by the host enzyme PARP1. PARP1, or Poly(ADP-ribose) polymerase 1, catalyzes the transfer of a poly(ADP-ribose) (PAR) moiety from NAD+ onto acceptor proteins including itself, histone proteins, and CTCF. PARylation of CTCF by PARP1 can affect CTCF’s insulator activity, DNA binding capacity, and ability to form chromatin loops. Both PARP1 and CTCF have been implicated in the regulation of EBV latency and lytic reactivation. Thus, we predicted that pharmacological inhibition with PARP1 inhibitors would affect EBV latency type through a chromatin-specific mechanism. Here, we show that PARP1 and CTCF colocalize at specific sites throughout the EBV genome, and provide evidence to suggest that PARP1 acts to stabilize CTCF binding and maintain the open chromatin landscape at the active Cp promoter during type III latency. Further, PARP1 activity is important in maintaining latency type-specific viral gene expression. The data presented here provide a rationale for the use of PARP inhibitors in the treatment of EBV-associated cancers exhibiting type III latency, and could ultimately contribute to an EBV-specific treatment strategy for AIDS-related or post-transplant lymphomas.
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| Overall design |
Two biological replicates of LCL FAIRE or just sonicate DNA (input) were used to make ChIP-seq libraries. For peak calling we compare the FAIRE enrichment to the input signal.
This series includes PARP1 and CTCF ChIP-seq of EBV.
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| Contributor(s) |
Lupey-Green LN, Caruso LB, Madzo J, Martin KA, Tan Y, Hulse M, Tempera I |
| Citation(s) |
29976663, 35039491 |
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| Submission date |
Jun 14, 2018 |
| Last update date |
Feb 08, 2022 |
| Contact name |
Italo Tempera |
| E-mail(s) |
[email protected]
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| Phone |
2157071940
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| Organization name |
Temple University
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| Department |
Fels Institute
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| Lab |
PAHB Room 206
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| Street address |
3307 N. Broad Street, PAHB, Room 206
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19140 |
| Country |
USA |
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| Platforms (1) |
| GPL25190 |
Illumina HiSeq 2500 (Human gammaherpesvirus 4) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA476186 |
| SRA |
SRP150563 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE115829_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR (of BED, BEDGRAPH, BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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