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EB病毒通过重塑表观修饰来促进胃癌发生
2020-07-29 22:34

日本千叶大学Atsushi Kaneda、新加坡国立大学Patrick Tan等研队人员合作发现EB病毒通过重塑表观修饰来促进胃癌发生。该研究于2020年7月27日在线发表于《自然—遗传学》。

研究人员表示,EB病毒(EBV)与几种人类恶性肿瘤相关,包括8-10%的胃癌(GC)。通过全基因组范围内对GC细胞系、原发组织和正常胃样品的3D染色质拓扑分析,研究人员发现了EBV阳性GC特有的染色质结构域,并表现出异染色质到常染色质的转变以及与非整合EBV附加体的长期相互作用。
 
体外EBV感染足以重塑染色质拓扑结构并在与EBV相互作用的宿主基因组基因座上发挥功能,从而将H3K9me3+异染色质转化为H3K4me1+/ H3K27ac+二价态,并释放潜在的增强子来参与和激活附近的GC相关基因(例如TGFBR2和MZT1)。
 
因此,EBV阳性GC的高级表观型代表了一种新的致癌范例,其中非整合型病毒基因组可以直接改变宿主的表观遗传状况(“增强子感染”),从而促进原癌基因的活化和肿瘤的发生。
 
附:英文原文

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

Author: Atsushi Okabe, Kie Kyon Huang, Keisuke Matsusaka, Masaki Fukuyo, Manjie Xing, Xuewen Ong, Takayuki Hoshii, Genki Usui, Motoaki Seki, Yasunobu Mano, Bahityar Rahmutulla, Teru Kanda, Takayoshi Suzuki, Sun Young Rha, Tetsuo Ushiku, Masashi Fukayama, Patrick Tan, Atsushi Kaneda

Issue&Volume: 2020-07-27

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.

DOI: 10.1038/s41588-020-0665-7

Source: https://www.nature.com/articles/s41588-020-0665-7

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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