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| Status |
Public on Mar 12, 2024 |
| Title |
Shared and distinct interactions of Epstein-Barr Nuclear Antigen 2 type 1 and type 2 with the human genome (RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
There are two major types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) like RBPJ, EBF1, and SPI1, type 2 EBNA2 shares only ~50% amino acid identity and may have distinct effects on the genome. In this study, we examined EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Our analyses revealed that both types 1 and 2 EBNA2 strongly bind to SPI1 and AP-1 motifs (BATF and JUNB). However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 with RBPJ. These differences in b hTF co-occupancy revealed type-specific gene expression of known EBNA2 targets. Both type 1 and 2 EBNA2 binding events were highly enriched at systemic lupus erythematosus (SLE) and showed type-specific enrichment at the risk loci of multiple sclerosis (type 1) and primary biliary cholangitis (type 2). Collectively, this study reveals extensive type-specific EBNA2 interactions with the human genome, genotype-dependent binding, and distinct associations with autoimmune disorders. Our results highlight the importance of considering EBV type in disease-related investigations.
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| Overall design |
We performed RNA-seq in AG876, Jiyoye, GM12878, Mutu, and Akata cell lines. Experiments were performed in three replicates per cell line.
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| Contributor(s) |
Weirauch M, Kottyan L |
| Citation(s) |
38475709 |
| |
| Submission date |
Oct 23, 2023 |
| Last update date |
Mar 20, 2024 |
| Contact name |
Matthew Weirauch |
| E-mail(s) |
Matthew.Weirauch@cchmc.org
|
| Organization name |
Cincinnati Children's Hospital Medical Center
|
| Department |
Center for Autoimmune Genomics and Etiology (CAGE)
|
| Street address |
3333 Burnet Avenue
|
| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229-3026 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE246062 |
Shared and distinct interactions of Epstein-Barr Nuclear Antigen 2 type 1 and type 2 with the human genome |
|
| Relations |
| BioProject |
PRJNA1031215 |
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