Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus

Abstract Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of mult...

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Autores principales:	Atsushi Okabe, Sayaka Funata, Keisuke Matsusaka, Hiroe Namba, Masaki Fukuyo, Bahityar Rahmutulla, Motohiko Oshima, Atsushi Iwama, Masashi Fukayama, Atsushi Kaneda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/259f6969d1784586ba7b0a61a019ae80
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spelling	oai:doaj.org-article:259f6969d1784586ba7b0a61a019ae802021-12-02T12:30:26ZRegulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus10.1038/s41598-017-08370-72045-2322https://doaj.org/article/259f6969d1784586ba7b0a61a019ae802017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08370-7https://doaj.org/toc/2045-2322Abstract Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis. We performed ChIP sequencing on H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K9me3 in gastric epithelial cells infected or not with EBV. We showed that repressive marks were redistributed after EBV infection, resulting in aberrant enhancer activation and repression. Enhancer dysfunction led to the activation of pathways related to cancer hallmarks (e.g., resisting cell death, disrupting cellular energetics, inducing invasion, evading growth suppressors, sustaining proliferative signalling, angiogenesis, and tumour-promoting inflammation) and inactivation of tumour suppressive pathways. Deregulation of cancer-related genes in EBV-infected gastric epithelial cells was also observed in clinical EBV(+) gastric cancer specimens. Our analysis showed that epigenetic alteration associated with EBV-infection may contribute to tumorigenesis through enhancer activation and repression.Atsushi OkabeSayaka FunataKeisuke MatsusakaHiroe NambaMasaki FukuyoBahityar RahmutullaMotohiko OshimaAtsushi IwamaMasashi FukayamaAtsushi KanedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atsushi Okabe Sayaka Funata Keisuke Matsusaka Hiroe Namba Masaki Fukuyo Bahityar Rahmutulla Motohiko Oshima Atsushi Iwama Masashi Fukayama Atsushi Kaneda Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus
description	Abstract Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis. We performed ChIP sequencing on H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K9me3 in gastric epithelial cells infected or not with EBV. We showed that repressive marks were redistributed after EBV infection, resulting in aberrant enhancer activation and repression. Enhancer dysfunction led to the activation of pathways related to cancer hallmarks (e.g., resisting cell death, disrupting cellular energetics, inducing invasion, evading growth suppressors, sustaining proliferative signalling, angiogenesis, and tumour-promoting inflammation) and inactivation of tumour suppressive pathways. Deregulation of cancer-related genes in EBV-infected gastric epithelial cells was also observed in clinical EBV(+) gastric cancer specimens. Our analysis showed that epigenetic alteration associated with EBV-infection may contribute to tumorigenesis through enhancer activation and repression.
format	article
author	Atsushi Okabe Sayaka Funata Keisuke Matsusaka Hiroe Namba Masaki Fukuyo Bahityar Rahmutulla Motohiko Oshima Atsushi Iwama Masashi Fukayama Atsushi Kaneda
author_facet	Atsushi Okabe Sayaka Funata Keisuke Matsusaka Hiroe Namba Masaki Fukuyo Bahityar Rahmutulla Motohiko Oshima Atsushi Iwama Masashi Fukayama Atsushi Kaneda
author_sort	Atsushi Okabe
title	Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus
title_short	Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus
title_full	Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus
title_fullStr	Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus
title_full_unstemmed	Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus
title_sort	regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by epstein-barr virus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/259f6969d1784586ba7b0a61a019ae80
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Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus

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