The Epstein–Barr virus lytic cycle activator Zta interacts with methylated ZRE in the promoter of host target gene egr1

Abstract

Activation of the host geneegr1is essential for the lytic replication of Epstein–Barr virus (EBV).egr1is 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 theegr1promoter and identify a weak interaction withegr1ZRE that is dependent on the distal part ofegr1ZRE. Furthermore, we demonstrate that the ability of Zta to interact withegr1ZRE is enhanced at least tenfold by methylation. The ability of Zta to transactivate a reporter construct driven by theegr1promoter 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 geneBRLF1, this suggests that Zta may also have the capability to overturn epigenetic control ofegr1.