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. 2013 Aug 27:4:161.
doi: 10.3389/fgene.2013.00161. eCollection 2013.

Epigenetic control of Epstein-Barr virus transcription - relevance to viral life cycle?

Alison J Sinclair  1
Affiliations

Epigenetic control of Epstein-Barr virus transcription - relevance to viral life cycle?

Alison J Sinclair. Front Genet. .

Abstract

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.

Keywords: CpG-DNA methylation; DNA binding; Epstein–Barr virus; cancer; replication cycle; transcription factor.

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Figures

FIGURE 1
FIGURE 1
The biphasic DNA methylation cycle of the EBV genome and its impact of ZREs. The colored bar depicts the methylation state of EBV genome during different phases of the viral life cycle, with non-methylated DNA in red and methylated DNA represented in green. Two types of Zta-responsive gene are shown below: those containing ZREs that are independent of DNA methylation (blue) and those that are dependent on methylation (white). Note that non-methylated CpG-ZREs cannot be bound by Zta. Periods where Zta is expressed are indicated in blue.
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