title: The reversal of epigenetic silencing of the EBV genome is regulated by viral bZIP protein.
abstract: 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.
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, UK.
authors.forename: Questa H
authors.initials: QH
authors.lastname: Karlsson
authors.forename: Celine
authors.initials: C
authors.lastname: Schelcher
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Verrall
authors.forename: Carlo
authors.initials: C
authors.lastname: Petosa
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Sinclair
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D020868:Gene Silencing; D016679:Genome, Viral / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D050976:Basic-Leucine Zipper Transcription Factors; D015534:Trans-Activators