Year: 2020
Type: article
Abstract: Epstein-Barr virus (EBV) genomes persist in latently infected cells as extrachromosomal episomes that attach to host chromosomes through the tethering functions of EBNA1, a viral encoded sequence-specific DNA binding protein. Here we employ circular chromosome conformation capture (4C) analysis to identify genome-wide associations between EBV episomes and host chromosomes. We find that EBV episomes in Burkitt's lymphoma cells preferentially associate with cellular genomic sites containing EBNA1 binding sites enriched with B-cell factors EBF1 and RBP-jK, the repressive histone mark H3K9me3, and AT-rich flanking sequence. These attachment sites correspond to transcriptionally silenced genes with GO enrichment for neuronal function and protein kinase A pathways. Depletion of EBNA1 leads to a transcriptional de-repression of silenced genes and reduction in H3K9me3. EBV attachment sites in lymphoblastoid cells with different latency type show different correlations, suggesting that host chromosome attachment sites are functionally linked to latency type gene expression programs.
Source: Nature Communications
Institutions: Chung-Ang University, University of Oregon, The Wistar Institute
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: U.S. Department of Health and Human Services, National Research Foundation, National Research Foundation of Korea, Ministry of Science and ICT, South Korea, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Dental and Craniofacial Research
Awards: G1033967322, G1634253349, Epigenetics of Aging and Age-associated Diseases, G173096298, G194090134, G2009932285, G3108696386, G3285340444, G3820147285, Condensin connects 3D genome organization, chromosomal segregation, and gene regulation via its interactions with transcription-related factors., G4723747710, G5187425790, G546097474, G5988931377, G606827912, G794535955, G8344155380, G9000181507, G9000307965, Epigenetic Regulation of Epstein-Barr Virus, Consolidated Basic Cancer Research Program
OpenAlex ID: W3006258484