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Moodle:

https://md.kumamoto-u.ac.jp/course/view.php?id=78273

 

Virus rewires chromatin structures and enhancers of host cells to induce tumorigenesis

 

Atsushi Kaneda

Department of Molecular Oncology, Graduate School of Medicine, Chiba University

 

Gastric cancer (GC) is stratified into several molecular subtypes. A subset of GC associated with Epstein-Barr virus (EBV) infection exhibits a unique epigenotype, including the most extensive DNA hypermethylation pattern in the all human malignancies. EBV infection itself was shown to cause DNA methylation induction in >3,000 promoter CpG islands, resulting in inactivation of tumor suppressor genes e.g. p16 and SHP1. Compirehensive analysis of 3D chromatin topologies by Hi-C revealed unique compartment changes in EBV GC. Episomal EBV DNA interacting human genome remodels chromatin topology, converting a part of H3K9me3(+) heterochromatin to H3K4me1(+)/H3K27ac(+) euchromatin, and unleashing latent enhancers to engage and activate neighboring GC-related genes. Viral genome thus alters host epigenetic landscapes by a new mechanism “enhancer infestation”, suggesting importance of virus as a driver of epigenetic tumorigenesis.

 

Key publications:

  1. Nat Genet. 52(9):919-930, 2020
  2. J Pathol. 242(4):391-399, 2017
  3. Nat Microbiol. 1:16026, 2016
  4. Cancer Res. 71(23):7187-97, 2011