EBV (Epstein–Barr virus) alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and in the switch to the lytic cycle this epigenetic silencing is overturned. A key event is the activation of the viral protein Zta with three ZREs (Zta-response elements) from the BRLF1 promoter (referred to as Rp). Two of these ZREs contain CpG motifs and are methylated in the latent genome. Biochemical analyses and molecular modelling of Zta bound to methylated RpZRE3 indicate the precise contacts made between a serine and a cysteine residue of Zta with methyl cytosines. A single point mutant of Zta, C189S, is defective in binding to the methylated ZREs both in vitro and in vivo. This was used to probe the functional relevance of the interaction. ZtaC189S was not able to activate Rp in a B-cell line, demonstrating the relevance of the interaction with methylated ZREs. This demonstrates that Zta plays a role in overturning the epigenetic control of viral latency.
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August 2008
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Conference Article|
July 22 2008
The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein
Questa H. Karlsson;
Questa H. Karlsson
1
*School of Life Sciences, University of Sussex, Brighton BN1 9QG, U.K.
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Celine Schelcher;
Celine Schelcher
1
*School of Life Sciences, University of Sussex, Brighton BN1 9QG, U.K.
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Elizabeth Verrall;
Elizabeth Verrall
*School of Life Sciences, University of Sussex, Brighton BN1 9QG, U.K.
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Carlo Petosa;
Carlo Petosa
†EMBL Grenoble, BP 181, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France
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Alison J. Sinclair
Alison J. Sinclair
2
*School of Life Sciences, University of Sussex, Brighton BN1 9QG, U.K.
2To whom correspondence should be addressed (email A.J.Sinclair@Sussex.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 01 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (4): 637–639.
Article history
Received:
April 01 2008
Citation
Questa H. Karlsson, Celine Schelcher, Elizabeth Verrall, Carlo Petosa, Alison J. Sinclair; The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein. Biochem Soc Trans 1 August 2008; 36 (4): 637–639. doi: https://doi.org/10.1042/BST0360637
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