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The Epstein-Barr Virus Regulome in Lymphoblastoid Cells.
Jiang, Sizun; Zhou, Hufeng; Liang, Jun; Gerdt, Catherine; Wang, Chong; Ke, Liangru; Schmidt, Stefanie C S; Narita, Yohei; Ma, Yijie; Wang, Shuangqi; Colson, Tyler; Gewurz, Benjamin; Li, Guoliang; Kieff, Elliott; Zhao, Bo.
Afiliação
  • Jiang S; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Zhou H; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Liang J; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Gerdt C; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Wang C; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Ke L; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Nasopharyngeal Carcinoma, Sun Yat-Sen Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
  • Schmidt SCS; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Narita Y; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Ma Y; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Wang S; National Key Laboratory of Crop Genetic Improvement, College of Life Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • Colson T; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Gewurz B; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Li G; National Key Laboratory of Crop Genetic Improvement, College of Life Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • Kieff E; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ekieff@bwh.harvard.edu.
  • Zhao B; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: bzhao@bwh.harvard.edu.
Cell Host Microbe ; 22(4): 561-573.e4, 2017 Oct 11.
Article em En | MEDLINE | ID: mdl-29024646
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Cromatina / Herpesvirus Humano 4 / Interações Hospedeiro-Patógeno Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Host Microbe Assunto da revista: MICROBIOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Cromatina / Herpesvirus Humano 4 / Interações Hospedeiro-Patógeno Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Host Microbe Assunto da revista: MICROBIOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos