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Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding

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posted on 2023-06-09, 00:19 authored by Nicolae Balan, Kay OsbornKay Osborn, Alison Sinclair
Repression of the cellular CIITA gene is part of the immune evasion strategy of the ?herpes virus Epstein-Barr virus (EBV) during its lytic replication cycle in B-cells. In part this is mediated through down regulation of MHC class II gene expression via the targeted repression of CIITA, the cellular master regulator of MHC class II gene expression. The repression is achieved through a reduction in CIITA promoter activity initiated by the EBV transcription and replication factor Zta (BZLF1, 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 CIITA promoter. We find that repression by Zta is specific for the CIITA 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 CIITA promoter without direct DNA binding comes from promoter mapping that shows that repression does not require the presence of a ZRE in the CIITA promoter.

Funding

Deciphering the complex mechanisms that reprogram gene expression during Epstein Barr Virus replicat; G0803; MRC; MR/J001708/1

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of General Virology

ISSN

0022-1317

Publisher

Microbiology Society

Volume

97

Page range

725-732

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-02-17

First Open Access (FOA) Date

2016-02-17

First Compliant Deposit (FCD) Date

2016-02-17

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