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- Title
Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome.
- Authors
Viel, Kenyatta C. M. F.; Parameswaran, Sreeja; Donmez, Omer A.; Forney, Carmy R.; Hass, Matthew R.; Yin, Cailing; Jones, Sydney H.; Prosser, Hayley K.; Diouf, Arame A.; Gittens, Olivia E.; Edsall, Lee E.; Chen, Xiaoting; Rowden, Hope; Dunn, Katelyn A.; Guo, Rui; VonHandorf, Andrew; Leong, Merrin Man Long; Ernst, Kevin; Kaufman, Kenneth M.; Lawson, Lucinda P.
- Abstract
Background: There are two major genetic 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) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. Results: In this study, we examined genome-wide 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. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. Conclusions: This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.
- Subjects
GENE expression; SYSTEMIC lupus erythematosus; MYC oncogenes; REGULATOR genes; ANTIGENS
- Publication
BMC Genomics, 2024, Vol 25, Issue 1, p1
- ISSN
1471-2164
- Publication type
Article
- DOI
10.1186/s12864-024-10183-8