Papillomavirus E2 Proteins and the Host Brd4 Protein Associate with Transcriptionally Active Cellular Chromatin
Papillomavirus E2 Proteins and the Host Brd4 Protein Associate with Transcriptionally Active Cellular Chromatin
复制标题
DOI：
10.1128/jvi.02275-08
复制
发表时间：
2009-03-15
影响因子：
5.4
通讯作者：
McBride, Alison A.
中科院分区：
文献类型：
--
作者：
Jang, Moon Kyoo;Kwon, Deukwoo;McBride, Alison A.
乳头瘤病毒E2蛋白与细胞Brd 4蛋白的相互作用对于病毒基因的转录调控和病毒基因组的分配是重要的。牛乳头瘤病毒1型（BPV-1）E2在有丝分裂和间期细胞中与Brd 4复合结合细胞染色质。为了鉴定细胞染色质上E2相互作用的特定位点，使用人类启动子序列进行全基因组染色质免疫沉淀芯片分析。在C33 A细胞中，发现E2和Brd 4都与大多数转录活性启动子结合。这些启动子也被RNA聚合酶II结合，并被组蛋白H3乙酰化和K4三甲基化修饰，所有这些都是活跃转录的指标。E2结合强烈相关的Brd 4和RNA聚合酶II占用和H3 K4 me 3修饰在所有人类启动子，表明E2结合到活跃的启动子。E2结合与启动子中存在的一致E2结合位点无关。此外，E2结合的细胞基因的mRNA水平没有显着改变E2的表达。因此，乳头瘤病毒E2蛋白结合转录活性细胞基因，但不改变其活性。我们认为这可能是病毒确保病毒基因组保留在细胞核转录活性区域以逃避沉默的一种方式。因此，E2介导的病毒基因组与宿主染色质的拴系具有多种作用：将病毒基因组分配给子细胞，确保基因组保留在细胞核中，并确保基因组保留在功能活性核结构域中。
The interaction of papillomavirus E2 proteins with cellular Brd4 protein is important for transcriptional regulation of viral genes and partitioning of viral genomes. Bovine papillomavirus type 1 (BPV-1) E2 binds cellular chromatin in complex with Brd4 in both mitotic and interphase cells. To identify specific sites of E2 interaction on cellular chromatin, a genome-wide chromatin immunoprecipitation-on-chip analysis was carried out using human promoter sequences. Both E2 and Brd4 were found bound to most transcriptionally active promoters in C33A cells. These promoters were also bound by RNA polymerase II and were modified by histone H3 acetylation and K4 trimethylation, all indicators of active transcription. E2 binding strongly correlated with Brd4 and RNA polymerase II occupancy and H3K4me3 modification at all human promoters, indicating that E2 bound to active promoters. E2 binding did not correlate with the presence of consensus E2 binding sites in the promoters. Furthermore, the mRNA levels of E2-bound cellular genes were not significantly changed by E2 expression. Thus, the papillomavirus E2 proteins bind to transcriptionally active cellular genes but do not change their activity. We propose that this may be a way for the virus to ensure that the viral genome is retained in transcriptionally active regions of the nucleus to escape silencing. Therefore, E2-mediated tethering of viral genomes to host chromatin has multiple roles: to partition the viral genome to daughter cells, to ensure that the genomes are retained in the nucleus, and to make certain that the genomes are retained in functionally active nuclear domains.