Evaluation of a prediction protocol to identify potential targets of epigenetic reprogramming by the cancer associated Epstein Barr virus.
Evaluation of a prediction protocol to identify potential targets of epigenetic reprogramming by the cancer associated Epstein Barr virus.
复制标题
DOI：
10.1371/journal.pone.0009443
复制
发表时间：
2010-02-26
期刊：
影响因子：
3.7
通讯作者：
Sinclair AJ
中科院分区：
文献类型：
--
作者：
Flower K;Hellen E;Newport MJ;Jones S;Sinclair AJ
爱泼斯坦巴尔病毒（EBV）感染大多数人类，与环境因素结合在一起在小比例中引起致命疾病。在初次感染后，EBV在记忆B细胞群中终生潜伏。病毒的反复再活化发生，可能是由于记忆B淋巴细胞的活化，导致病毒复制和B淋巴细胞的再感染。CpG基序处病毒DNA的甲基化导致潜伏期期间病毒基因表达的沉默。Zta是介导潜伏/再激活平衡的关键病毒蛋白，与甲基化DNA相互作用。Zta是病毒和宿主基因的转录因子。其DNA结合位点（ZRE）的子集包含CpG基序，其以其甲基化形式被识别。对病毒基因BRLF 1启动子的详细分析显示，与甲基化CpG ZRE（RpZRE 3）的相互作用是推翻该基因表观遗传沉默的关键。在这里，我们的问题，我们是否可以使用这些信息来确定哪些宿主基因含有类似的响应元件的启动子。人类基因启动子的计算搜索确定了274个含有7个核苷酸RpZRE 3核心元件的靶标。Zta与其中17个靶标的DNA结合分析显示，核心元件的侧翼背景对Zta与甲基化位点相互作用的能力没有深刻的影响。观察到一个启动子的第二个并列的ZRE。Zta能够与该位点相互作用，尽管没有观察到与RpZRE 3核心元件的共占据。这项研究表明，274个人类启动子有可能受到Zta的调控，从而在病毒从潜伏期重新激活期间推翻基因表达的表观遗传沉默。
Epstein Barr virus (EBV) infects the majority of the human population, causing fatal diseases in a small proportion in conjunction with environmental factors. Following primary infection, EBV remains latent in the memory B cell population for life. Recurrent reactivation of the virus occurs, probably due to activation of the memory B-lymphocytes, resulting in viral replication and re-infection of B-lymphocytes. Methylation of the viral DNA at CpG motifs leads to silencing of viral gene expression during latency. Zta, the key viral protein that mediates the latency/reactivation balance, interacts with methylated DNA. Zta is a transcription factor for both viral and host genes. A sub-set of its DNA binding sites (ZREs) contains a CpG motif, which is recognised in its methylated form. Detailed analysis of the promoter of the viral gene BRLF1 revealed that interaction with a methylated CpG ZRE (RpZRE3) is key to overturning the epigenetic silencing of the gene. Here we question whether we can use this information to identify which host genes contain promoters with similar response elements. A computational search of human gene promoters identified 274 targets containing the 7-nucleotide RpZRE3 core element. DNA binding analysis of Zta with 17 of these targets revealed that the flanking context of the core element does not have a profound effect on the ability of Zta to interact with the methylated sites. A second juxtaposed ZRE was observed for one promoter. Zta was able to interact with this site, although co-occupancy with the RpZRE3 core element was not observed. This research demonstrates 274 human promoters have the potential to be regulated by Zta to overturn epigenetic silencing of gene expression during viral reactivation from latency.
登录
查看更多内容
影响因子：
5.4
作者：
Feng, WH;Hong, G;Kenney, SC
通讯作者：
Kenney, SC
影响因子：
4.8
作者：
Jones, Richard J.;Dickerson, Sarah;Kenney, Shannon C.
通讯作者：
Kenney, Shannon C.
影响因子：
5.4
作者：
Hsu, Meichi;Wu, Shih-Yi;Chang, Yao
通讯作者：
Chang, Yao
影响因子：
3.8
作者：
ERNBERG, I;FALK, K;KLEIN, G
通讯作者：
KLEIN, G
DOI：
10.1099/vir.0.007922-0
发表时间：
2009-06
期刊：
The Journal of general virology
影响因子：
--
作者：
Heather J;Flower K;Isaac S;Sinclair AJ
通讯作者：
Sinclair AJ