The Epstein-Barr virus lytic cycle activator Zta interacts with methylated ZRE in the promoter of host target gene egr1.
Activation of the host gene egr1 is essential for the lytic replication of Epstein-Barr virus (EBV). egr1 is activated by Zta (BZLF1, ZEBRA). Zta interacts directly with DNA through a series of closely related Zta-response elements (ZREs). Here we dissect the mechanism used by Zta to interact with the egr1 promoter and identify a weak interaction with egr1ZRE that is dependent on the distal part of egr1ZRE. Furthermore, we demonstrate that the ability of Zta to interact with egr1ZRE is enhanced at least tenfold by methylation. The ability of Zta to transactivate a reporter construct driven by the egr1 promoter can be enhanced by methylation. As the ability of Zta to interact with a methylated ZRE in the EBV genome correlates with its ability to activate the expression of the endogenous viral gene BRLF1, this suggests that Zta may also have the capability to overturn epigenetic control of egr1.
Heather
James
J
School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
Flower
Kirsty
K
School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
Isaac
Samine
S
School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
Sinclair
Alison J
AJ
School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D017930:Genes, Reporter; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008745:Methylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D014779:Virus Replication
C063676:BZLF1 protein, Herpesvirus 4, Human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D015534:Trans-Activators; D004247:DNA