Epigenetic control of Epstein-Barr virus transcription - relevance to viral life cycle?
Epigenetic control of Epstein-Barr virus transcription - relevance to viral life cycle?
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DOI：
10.3389/fgene.2013.00161
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发表时间：
2013
影响因子：
3.7
通讯作者：
Sinclair AJ
中科院分区：
文献类型：
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作者：
Sinclair AJ
DNA甲基化通常会导致基因表达沉默，但EB病毒(EBV)提供了表观遗传学范式的例外。DNA甲基化是许多病毒基因表达所必需的。虽然病毒基因组最初在新感染的细胞中没有甲基化，但在病毒潜伏期的建立过程中，它变得广泛的甲基化。EBV基因表达的主要调控因子之一是一种称为Zta(BZLF1，Zebra，Z)的病毒转录因子，它类似于细胞内的AP1转录因子。Zta识别至少32个7核苷酸DNA序列元件的变体，即Zta反应元件(ZRE)，其中一些包含CpG基序。Zta只以DNA甲基化的形式与后一类ZRE结合，无论它们存在于病毒还是细胞启动子中，并且在功能上与这些启动子的活性相关。Zta解释病毒基因组差异DNA甲基化的能力对于病毒潜伏期的建立和从潜伏期中释放以启动病毒复制都是至关重要的。
DNA methylation normally leads to silencing of gene expression but Epstein–Barr virus (EBV) provides an exception to the epigenetic paradigm. DNA methylation is absolutely required for the expression of many viral genes. Although the viral genome is initially un-methylated in newly infected cells, it becomes extensively methylated during the establishment of viral latency. One of the major regulators of EBV gene expression is a viral transcription factor called Zta (BZLF1, ZEBRA, Z) that resembles the cellular AP1 transcription factor. Zta recognizes at least 32 variants of a 7-nucleotide DNA sequence element, the Zta-response element (ZRE), some of which contain a CpG motif. Zta only binds to the latter class of ZREs in their DNA-methylated form, whether they occur in viral or cellular promoters and is functionally relevant for the activity of these promoters. The ability of Zta to interpret the differential DNA methylation of the viral genome is paramount for both the establishment of viral latency and the release from latency to initiate viral replication.