Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome

Autor: Kenyatta C. M. F. Viel, Sreeja Parameswaran, Omer A. Donmez, Carmy R. Forney, Matthew R. Hass, Cailing Yin, Sydney H. Jones, Hayley K. Prosser, Arame A. Diouf, Olivia E. Gittens, Lee E. Edsall, Xiaoting Chen, Hope Rowden, Katelyn A. Dunn, Rui Guo, Andrew VonHandorf, Merrin Man Long Leong, Kevin Ernst, Kenneth M. Kaufman, Lucinda P. Lawson, Ben Gewurz, Bo Zhao, Leah C. Kottyan, Matthew T. Weirauch
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Genomics, Vol 25, Iss 1, Pp 1-21 (2024)
Druh dokumentu: article
ISSN: 1471-2164
DOI: 10.1186/s12864-024-10183-8
Popis: 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.
Databáze: Directory of Open Access Journals
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