RRC ID 62959
Author Okabe A, Huang KK, Matsusaka K, Fukuyo M, Xing M, Ong X, Hoshii T, Usui G, Seki M, Mano Y, Rahmutulla B, Kanda T, Suzuki T, Rha SY, Ushiku T, Fukayama M, Tan P, Kaneda A.
Title Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma.
Journal Nat Genet
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.
Volume 52(9)
Pages 919-930
Published 2020-9-1
DOI 10.1038/s41588-020-0665-7
PII 10.1038/s41588-020-0665-7
PMID 32719515
MeSH Adenocarcinoma / genetics* Adenocarcinoma / virology* Carcinogenesis / genetics Cell Line, Tumor Chromatin / genetics* Epigenomics / methods Epstein-Barr Virus Infections / genetics* Herpesvirus 4, Human / genetics* Humans Proto-Oncogene Mas Stomach Neoplasms / genetics* Stomach Neoplasms / virology* Transcription, Genetic / genetics*
IF 27.605
Human and Animal Cells MKN7(RCB0999)