机构：[1]Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA;[2]Harvard Med Sch, Boston, MA 02115 USA;[3]Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA;[4]Sun Yat Sen Univ, Sun Yat Sen Canc Ctr, Dept Nasopharyngeal Carcinoma, Guangzhou 510060, Guangdong, Peoples R China;临床科室鼻咽科中山大学肿瘤防治中心[5]Huazhong Agr Univ, Coll Life Sci & Technol, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Hubei, Peoples R China
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers. Deleting EBNA2 sites significantly reduced their target gene expression. Additional EBV super-enhancer (ESE) targets included MCL1, IRF4, and EBF. MYC ESE looping to the transcriptional stat site of MYC was dependent on EBNAs. Deleting MYC ESEs greatly reduced MYC expression and LCL growth. EBNA3A/3C altered CDKN2A/B spatial organization to suppress senescence. EZH2 inhibition decreased the looping at the CDKN2A/B loci and reduced LCL growth. This study provides a comprehensive view of the spatial organization of chromatin during EBV-driven cellular transformation.
基金：
National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI123420]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA047006, R01CA170023, R01CA085180]; Burroughs Wellcome Medical Scientist career award; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [91440114]
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外文
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出版当年[2017]版：
大类|1 区生物
小类|1 区微生物学1 区寄生虫学1 区病毒学
最新[2023]版：
大类|1 区医学
小类|1 区微生物学1 区寄生虫学1 区病毒学
第一作者：
第一作者机构：[1]Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA;[2]Harvard Med Sch, Boston, MA 02115 USA;[3]Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA;
通讯作者：
通讯机构：[1]Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA;[2]Harvard Med Sch, Boston, MA 02115 USA;[3]Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA;
生物