1887

Abstract

Repression of the cellular gene is part of the immune evasion strategy of the γherpes virus Epstein–Barr virus (EBV) during its lytic replication cycle in B-cells. In part, this is mediated through downregulation of MHC class II gene expression via the targeted repression of , the cellular master regulator of MHC class II gene expression. This repression is achieved through a reduction in promoter activity, initiated by the EBV transcription and replication factor, Zta (, EB1, ZEBRA). Zta is the earliest gene expressed during the lytic replication cycle. Zta interacts with sequence-specific elements in promoters, enhancers and the replication origin (ZREs), and also modulates gene expression through interaction with cellular transcription factors and co-activators. Here, we explore the requirements for Zta-mediated repression of the promoter. We find that repression by Zta is specific for the promoter and can be achieved in the absence of other EBV genes. Surprisingly, we find that the dimerization region of Zta is not required to mediate repression. This contrasts with an obligate requirement of this region to correctly orientate the DNA contact regions of Zta to mediate activation of gene expression through ZREs. Additional support for the model that Zta represses the promoter without direct DNA binding comes from promoter mapping that shows that repression does not require the presence of a ZRE in the promoter.

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2016-03-01
2020-01-22
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