Cutting edge Seminar
※ Zoom online/ Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle
Speaker: Atsushi Kaneda (Professor, Department of Molecular Oncology, Graduate School of Medicine, Chiba University)
Title: Virus rewires chromatin structures and enhancers of host cells to induce tumorigenesis
Date&Time: 17 Feb. (Wed.) 2021, 12:00- 13:00
Venue: Zoom online/ Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle
Abstract:
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, 201