报告题目：The Genomic Landscape of Epstein–Barrvirus nuclear antigens in Lymphoblastoid B Cells

报告人：周胡峰 教授

报告时间：2016年10月19日（周三）14:30

报告地点：逸夫楼C座314会议室

摘要：

Epstein–Barrvirus (EBV) nuclear antigens including EBNALP (LP), EBNA3A(E3A), EBNA3C(E3C)and EBNA2 (E2) are coexpressed in EBV-infected B lymphocytes and are criticalfor lymphoblastoid cell line outgrowth. LP removes NCOR and RBPJ repressivecomplexes from promoters, enhancers, and matrix-associated deacetylase bodies,whereas E2 activates transcription from distal enhancers. Our studies show thatLP/E2 sites were more similar to LP than to E2 sites in associated cell TFs,RNAPII, P300, and histone H3K4me3, H3K9ac, H3K27ac, and H2Az occupancy, andwere more highly transcribed than LP or E2 sites. Gene affected by CTCF and LPcooccupancy were more highly expressed than genes affected by CTCF alone. LPwas at myc enhancers and promotersand MYC regulated cell survival genes. EBNA3Asites clustered into seven unique groups, with differing B-cell TFs andepigenetic marks. EBNA3A coincidence with BATF-IRF4 or RUNX3 was associatedwith stronger EBNA3A ChIP-Seq signals. EBNA3A was at MYC,CDKN2A/B, CCND2,CXCL9/10, and BCL2, together with RUNX3, BATF, IRF4, and SPI1. EBNA3C signals were strongestat BATF/IRF4 and SPI1/IRF4 composite sites. EBNA3C bound strongly to the p14ARF promoter through SPI1/IRF4/BATF/RUNX3, establishing RBPJ-, Sin3A-, andREST-mediated repression. These data implicate LP and associated TFs and DNAlooping factors CTCF, RAD21, and YY1chromatin remodeling complexes in repressordepletion and gene activation necessary for lymphoblastoid cell line growth andstrongly support a model in which EBNA3A and EBNA3C are tethered to DNA througha BATF-containing protein complexes to enable continuous cell proliferation.

Reference:

1) Daniel Portal*,Hufeng Zhou*, Bo Zhao, Peter V. Kharchenko, Elizabeth Lowry, Limsoon Wong, JohnQuackenbush et al. "Epstein–Barr virus nuclearantigen leader protein localizes to promoters and enhancers with celltranscription factors and EBNA2." Proceedings of the National Academy ofSciences 110, no. 46 (2013): 18537-18542.

2) Sizun Jiang,Bradford Willox, Hufeng Zhou, Amy M. Holthaus, Anqi Wang, Tommy T. Shi, SeijiMaruo et al. "Epstein–Barr Virus NuclearAntigen 3C binds to BATF/IRF4 or SPI1/IRF4 composite sites and recruits Sin3Ato repress CDKN2A." Proceedings of the National Academy of Sciences 111,no. 1 (2014): 421-426.

3) Schmidt, StefanieCS, Sizun Jiang, Hufeng Zhou, Bradford Willox, Amy M. Holthaus, PeterV.Kharchenko, Eric C. Johannsen, Elliott Kieff, and Bo Zhao. "Epstein–Barrvirus nuclear antigen 3A partially coincides with EBNA3C genome-wide and istethered to DNA through BATF complexes." Proceedings of the NationalAcademy of Sciences 112, no. 2 (2015): 554-559.

报告人简介：

周胡峰博士现担任哈佛医学院(Harvard Medical School)和哈佛附属医院(Brigham and Woman's Hospital)讲师。目前的研究兴趣主要有以下两个方向 (i) 下一代测序的临床应用, 包 括WholeExome Sequencing (WES) and Whole Genome Sequencing data analysis (WGS) dataanalysis. (ii) 基于下一代测序技探索 EBV 病毒的导致癌症的机理和 EBV 增强子的调控作用包括ChIP-Seq, RNA-seq, GRO-seq,HiC, ChIA-PET, 4C-seq, 等等. 此外,我有多年的研究蛋白质互做和预测的 Protein-Protein Interactions (PPI) 科研经历;Pathway 数据融合与分析经历; Human-Microbiome Metagenomic 经历; 以及相关科研课题的软件以及数据库开发经验。