期刊
NATURE GENETICS
卷 52, 期 9, 页码 919-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-020-0665-7
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资金
- Japan Agency for Medical Research and Development (AMED) [19ck0106263h0003, 19cm0106510h0004]
- Japan Society for the Promotion of Science [19H03726, 19K16101]
- Takeda Science Foundation
- Chiba University [2018-Y9]
- Duke-NUS Medical School grant [RL2016-080]
- National Medical Research Council [NMRC/STaR/0026/2015, OF-LCG18May-0023]
- Cancer Science Institute of Singapore
- National University of Singapore under the National Research Foundation Singapore
- Singapore Ministry of Education under its Research Centres of Excellence initiative
- Grants-in-Aid for Scientific Research [19H03726, 19K16101] Funding Source: KAKEN
Epstein-Barr virus (EBV) is associated with several human malignancies including 8-10% of gastric cancers (GCs). Genome-wide analysis of 3D chromatin topologies across GC lines, primary tissue and normal gastric samples revealed chromatin domains specific to EBV-positive GC, exhibiting heterochromatin-to-euchromatin transitions and long-range human-viral interactions with non-integrated EBV episomes. EBV infection in vitro suffices to remodel chromatin topology and function at EBV-interacting host genomic loci, converting H3K9me3(+)heterochromatin to H3K4me1(+)/H3K27ac(+)bivalency and unleashing latent enhancers to engage and activate nearby GC-related genes (for exampleTGFBR2andMZT1). Higher-order epigenotypes of EBV-positive GC thus signify a novel oncogenic paradigm whereby non-integrative viral genomes can directly alter host epigenetic landscapes ('enhancer infestation'), facilitating proto-oncogene activation and tumorigenesis. Genome-wide analysis of 3D chromatin topologies across gastric cancers suggests that Epstein-Barr virus infection may induce the epigenetic rewiring of EBV-positive tumors through human-viral chromatin interactions, a phenomenon termed 'enhancer infestation'.
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