Systematic investigation reveals extensive Epstein-Barr virus transcriptional regulation of the human genome
Year: 2026
Type: article
Abstract: We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (viral transcriptional regulators [vTRs]) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale profiling of vTR binding, chromatin accessibility alterations, and gene expression impact reveals extensive EBV functional interactions with the human genome, including >100,000 vTR binding events impacting almost a quarter of human genes. BMRF1 emerges as a potent regulator, impacting >7,000 genes and altering >37,000 chromatin regions. Our results reveal that EBV RTA interacts with and stabilizes the binding of human RBPJ. Network analysis reveals that many human genes are targeted by multiple EBV-vTRs, highlighting the vast coordinated impact of EBV on human gene expression. This study provides a valuable, extensive resource for examining EBV-induced alterations to human gene regulation, with data available on multiple platforms.
Source: Cell Genomics
Authors: Phillip J. Dexheimer, Matthew R. Hass, Lee E. Edsall, Arame A. Diouf, Sydney H. Jones, Omer Donmez, Cailing Yin, Katelyn A. Dunn, Carmy Forney, Hayley K. Hesse, Andrew VonHandorf, Xiaoting Chen, Sreeja Parameswaran, Olivia E. Gittens, Kenyatta C.M.F. Viel, Rozita Razavi, Benjamin E. Gewurz, Bo Zhao, Lucinda P. Lawson, Timothy R. Hughes, Leah C. Kottyan, Matthew T. Weirauch
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $8,900
Funders: Cincinnati Children's Hospital Medical Center, National Institutes of Health, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research
Awards: CisBP and CisBP-RNA: web resources for protein-DNA and protein-RNA binding models, Virus-driven human gene misregulation in disease, Genomics of Inflammatory Bowel Disease, Gene Regulation as a Foundation for Autoimmune Disease Prevention, Polygenic Risk Scores for Healthier African American Families, Transcription Factor Genetics in Lupus, G9000116733, G9000169229, Regulation of the Epstein-Barr Virus Lytic Switch, Cincinnati Rheumatic Diseases Resource Center, Genetic Linkage in Lupus, Cincinnati Training Program in Pediatric Rheumatology, Epithelial Genes in Allergic Inflammation, Molecular Mechanisms of the Dysregulated Immune Response to Ebola Virus, Binding of Epstein Barr Virus EBNA2 Unifies Multiple Sclerosis Genetic Mechanisms, Epstein-Barr Virus Driven Tonsillar Versus Peripheral B-cell One-Carbon Metabolic Network Remodeling
OpenAlex ID: W4412506172