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Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor.
PLoS One. 2011; 6(10):e25922.Plos

Abstract

Epstein-Barr virus (EBV) encoded transcription factor Zta (BZLF1, ZEBRA, EB1) is the prototype of a class of transcription factor (including C/EBPalpha) that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication. The requirement for CpG-methylation at critical Zta response elements (ZREs) has been proposed to regulate EBV replication, specifically it could aid the activation of viral lytic gene expression from silenced promoters on the methylated genome during latency in addition to preventing full lytic reactivation from the non-methylated EBV genome immediately following infection. We developed a computational approach to predict the location of ZREs which we experimentally assessed using in vitro and in vivo DNA association assays. A remarkably different binding motif is apparent for the CpG and non-CpG ZREs. Computational prediction of the location of these binding motifs in EBV revealed that the majority of lytic cycle genes have at least one and many have multiple copies of methylation-dependent CpG ZREs within their promoters. This suggests that the abundance of Zta protein coupled with the methylation status of the EBV genome act together to co-ordinate the expression of lytic cycle genes at the majority of EBV promoters.

Authors+Show Affiliations

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

22022468

Citation

Flower, Kirsty, et al. "Epigenetic Control of Viral Life-cycle By a DNA-methylation Dependent Transcription Factor." PloS One, vol. 6, no. 10, 2011, pp. e25922.
Flower K, Thomas D, Heather J, et al. Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor. PLoS ONE. 2011;6(10):e25922.
Flower, K., Thomas, D., Heather, J., Ramasubramanyan, S., Jones, S., & Sinclair, A. J. (2011). Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor. PloS One, 6(10), e25922. https://doi.org/10.1371/journal.pone.0025922
Flower K, et al. Epigenetic Control of Viral Life-cycle By a DNA-methylation Dependent Transcription Factor. PLoS ONE. 2011;6(10):e25922. PubMed PMID: 22022468.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor. AU - Flower,Kirsty, AU - Thomas,David, AU - Heather,James, AU - Ramasubramanyan,Sharada, AU - Jones,Susan, AU - Sinclair,Alison J, Y1 - 2011/10/11/ PY - 2011/06/27/received PY - 2011/09/13/accepted PY - 2011/10/25/entrez PY - 2011/10/25/pubmed PY - 2012/2/18/medline SP - e25922 EP - e25922 JF - PloS one JO - PLoS ONE VL - 6 IS - 10 N2 - Epstein-Barr virus (EBV) encoded transcription factor Zta (BZLF1, ZEBRA, EB1) is the prototype of a class of transcription factor (including C/EBPalpha) that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication. The requirement for CpG-methylation at critical Zta response elements (ZREs) has been proposed to regulate EBV replication, specifically it could aid the activation of viral lytic gene expression from silenced promoters on the methylated genome during latency in addition to preventing full lytic reactivation from the non-methylated EBV genome immediately following infection. We developed a computational approach to predict the location of ZREs which we experimentally assessed using in vitro and in vivo DNA association assays. A remarkably different binding motif is apparent for the CpG and non-CpG ZREs. Computational prediction of the location of these binding motifs in EBV revealed that the majority of lytic cycle genes have at least one and many have multiple copies of methylation-dependent CpG ZREs within their promoters. This suggests that the abundance of Zta protein coupled with the methylation status of the EBV genome act together to co-ordinate the expression of lytic cycle genes at the majority of EBV promoters. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22022468/Epigenetic_control_of_viral_life_cycle_by_a_DNA_methylation_dependent_transcription_factor_ L2 - http://dx.plos.org/10.1371/journal.pone.0025922 DB - PRIME DP - Unbound Medicine ER -