Department of Genetics, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22421-6. doi: 10.1073/pnas.0911676106. Epub 2009 Dec 22.
Epstein-Barr virus (EBV) is associated with several types of lymphomas and epithelial tumors including Burkitt's lymphoma (BL), HIV-associated lymphoma, posttransplant lymphoproliferative disorder, and nasopharyngeal carcinoma. EBV nuclear antigen 1 (EBNA1) is expressed in all EBV associated tumors and is required for latency and transformation. EBNA1 initiates latent viral replication in B cells, maintains the viral genome copy number, and regulates transcription of other EBV-encoded latent genes. These activities are mediated through the ability of EBNA1 to bind viral-DNA. To further elucidate the role of EBNA1 in the host cell, we have examined the effect of EBNA1 on cellular gene expression by microarray analysis using the B cell BJAB and the epithelial 293 cell lines transfected with EBNA1. Analysis of the data revealed distinct profiles of cellular gene changes in BJAB and 293 cell lines. Subsequently, chromatin immune-precipitation revealed a direct binding of EBNA1 to cellular promoters. We have correlated EBNA1 bound promoters with changes in gene expression. Sequence analysis of the 100 promoters most enriched revealed a DNA motif that differs from the EBNA1 binding site in the EBV genome.
EB 病毒（EBV）与多种淋巴瘤和上皮肿瘤有关，包括伯基特淋巴瘤（BL）、HIV 相关淋巴瘤、移植后淋巴组织增生性疾病和鼻咽癌。EBV 核抗原 1（EBNA1）在所有与 EBV 相关的肿瘤中均有表达，是潜伏期和转化所必需的。EBNA1 在 B 细胞中启动潜伏病毒复制，维持病毒基因组拷贝数，并调节其他 EBV 编码潜伏基因的转录。这些活性是通过 EBNA1 结合病毒-DNA 的能力介导的。为了进一步阐明 EBNA1 在宿主细胞中的作用，我们使用微阵列分析检查了 EBNA1 对 B 细胞 BJAB 和转染了 EBNA1 的上皮 293 细胞系中细胞基因表达的影响。数据分析显示，BJAB 和 293 细胞系中的细胞基因变化具有明显不同的特征。随后，染色质免疫沉淀显示 EBNA1 直接与细胞启动子结合。我们将 EBNA1 结合的启动子与基因表达的变化相关联。与最丰富的 100 个启动子相关联的序列分析揭示了一个不同于 EBV 基因组中 EBNA1 结合位点的 DNA 基序。
