| Literature DB >> 32719515 |
Atsushi Okabe1, Kie Kyon Huang2, Keisuke Matsusaka1, Masaki Fukuyo1, Manjie Xing3, Xuewen Ong2, Takayuki Hoshii1, Genki Usui1,4, Motoaki Seki1, Yasunobu Mano1, Bahityar Rahmutulla1, Teru Kanda5, Takayoshi Suzuki6, Sun Young Rha7, Tetsuo Ushiku4, Masashi Fukayama4, Patrick Tan8,9,10, Atsushi Kaneda11.
Abstract
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 example TGFBR2 and MZT1). 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.Entities:
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Year: 2020 PMID： 32719515 DOI： 10.1038/s41588-020-0665-7
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330