J. Virol.-2012-Ramasubramanyan-1809-19.pdf (1.77 MB)
Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome.
journal contributionposted on 2023-06-08, 09:25 authored by Sharada Ramasubramanyan, Kay OsbornKay Osborn, Kirsty Flower, Alison Sinclair
The ability of EBV to establish latency allows it to evade the immune system and to persist for the lifetime of its host; one distinguishing characteristic is the lack of transcription of the majority of viral genes. Entry into the lytic cycle is co-ordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, EB1) and downstream effectors, while viral genome replication requires the concerted action of Zta and six other viral proteins at the origins of lytic replication. Here we explore the chromatin context at key EBV lytic cycle promoters, the origins of lytic replication during latency and lytic replication. We show that a repressive heterochromatin-like environment (tri-methylation of histone H3 at lysine 9 (H3K9me3) and lysine 27 (H3K27me3)), which blocks the interaction of some transcription factors with DNA, encompasses the key early lytic regulatory regions. Epigenetic silencing of the EBV genome is also imposed by DNA methylation during latency. The chromatin environment changes during the lytic cycle with activation of histones H3, H4 and H2AX occurring at both the origins of replication and at the key lytic regulatory elements. We propose that Zta is able to reverse the effects of latency-associated repressive chromatin at EBV early lytic promoters by interacting with Zta response elements (ZREs) within the H3K9me3-associated chromatin and demonstrate that these interactions occur in vivo. As the interaction of Zta with DNA is not inhibited by DNA methylation, it is clear that Zta uses two routes to overcome epigenetic silencing of its genome.
- Published version
JournalJournal of Virology
PublisherAmerican Society of Microbiology
Department affiliated with
- Biochemistry Publications
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