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Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome.
J Virol. 2012 Feb; 86(3):1809-19.JV

Abstract

The ability of Epstein-Barr virus (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 coordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, and 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. We explored the chromatin context at key EBV lytic cycle promoters (BZLF1, BRLF1, BMRF1, and BALF5) and the origins of lytic replication during latency and lytic replication. We show that a repressive heterochromatin-like environment (trimethylation 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 within the H3K9me3-associated chromatin and demonstrate that these interactions occur in vivo. Since 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.

Authors+Show Affiliations

School of Life Sciences, University of Sussex, Brighton, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22090141

Citation

Ramasubramanyan, Sharada, et al. "Dynamic Chromatin Environment of Key Lytic Cycle Regulatory Regions of the Epstein-Barr Virus Genome." Journal of Virology, vol. 86, no. 3, 2012, pp. 1809-19.
Ramasubramanyan S, Osborn K, Flower K, et al. Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome. J Virol. 2012;86(3):1809-19.
Ramasubramanyan, S., Osborn, K., Flower, K., & Sinclair, A. J. (2012). Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome. Journal of Virology, 86(3), 1809-19. https://doi.org/10.1128/JVI.06334-11
Ramasubramanyan S, et al. Dynamic Chromatin Environment of Key Lytic Cycle Regulatory Regions of the Epstein-Barr Virus Genome. J Virol. 2012;86(3):1809-19. PubMed PMID: 22090141.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome. AU - Ramasubramanyan,Sharada, AU - Osborn,Kay, AU - Flower,Kirsty, AU - Sinclair,Alison J, Y1 - 2011/11/16/ PY - 2011/11/18/entrez PY - 2011/11/18/pubmed PY - 2012/4/10/medline SP - 1809 EP - 19 JF - Journal of virology JO - J. Virol. VL - 86 IS - 3 N2 - The ability of Epstein-Barr virus (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 coordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, and 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. We explored the chromatin context at key EBV lytic cycle promoters (BZLF1, BRLF1, BMRF1, and BALF5) and the origins of lytic replication during latency and lytic replication. We show that a repressive heterochromatin-like environment (trimethylation 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 within the H3K9me3-associated chromatin and demonstrate that these interactions occur in vivo. Since 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. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/22090141/Dynamic_chromatin_environment_of_key_lytic_cycle_regulatory_regions_of_the_Epstein_Barr_virus_genome_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=22090141 DB - PRIME DP - Unbound Medicine ER -