Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma

Nat Genet. 2020 Sep;52(9):919-930. doi: 10.1038/s41588-020-0665-7. Epub 2020 Jul 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Chromatin
  • MAS1 protein, human
  • Proto-Oncogene Mas