Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
BMC Genomics - 25(2024), 1, Seite 21 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kenyatta C. M. F. Viel [VerfasserIn] |
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| Links: |
doi.org [kostenfrei] |
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| Themen: |
Autoimmune disorders |
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| doi: |
10.1186/s12864-024-10183-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
DOAJ095670408 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Autoimmune disorders | |
| 650 | 4 | |a ChIP-seq | |
| 650 | 4 | |a EBNA2 | |
| 650 | 4 | |a EBV | |
| 650 | 4 | |a Functional genomics | |
| 650 | 4 | |a Gene regulation | |
| 653 | 0 | |a Biotechnology | |
| 653 | 0 | |a Genetics | |
| 700 | 0 | |a Sreeja Parameswaran |e verfasserin |4 aut | |
| 700 | 0 | |a Omer A. Donmez |e verfasserin |4 aut | |
| 700 | 0 | |a Carmy R. Forney |e verfasserin |4 aut | |
| 700 | 0 | |a Matthew R. Hass |e verfasserin |4 aut | |
| 700 | 0 | |a Cailing Yin |e verfasserin |4 aut | |
| 700 | 0 | |a Sydney H. Jones |e verfasserin |4 aut | |
| 700 | 0 | |a Hayley K. Prosser |e verfasserin |4 aut | |
| 700 | 0 | |a Arame A. Diouf |e verfasserin |4 aut | |
| 700 | 0 | |a Olivia E. Gittens |e verfasserin |4 aut | |
| 700 | 0 | |a Lee E. Edsall |e verfasserin |4 aut | |
| 700 | 0 | |a Xiaoting Chen |e verfasserin |4 aut | |
| 700 | 0 | |a Hope Rowden |e verfasserin |4 aut | |
| 700 | 0 | |a Katelyn A. Dunn |e verfasserin |4 aut | |
| 700 | 0 | |a Rui Guo |e verfasserin |4 aut | |
| 700 | 0 | |a Andrew VonHandorf |e verfasserin |4 aut | |
| 700 | 0 | |a Merrin Man Long Leong |e verfasserin |4 aut | |
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| 700 | 0 | |a Leah C. Kottyan |e verfasserin |4 aut | |
| 700 | 0 | |a Matthew T. Weirauch |e verfasserin |4 aut | |
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