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

Balan, Nicolae, Osborn, Kay and Sinclair, Alison J (2016) Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding. Journal of General Virology, 97. pp. 725-732. ISSN 0022-1317

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Repression of the cellular CIITA 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 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0450 Physical and theoretical chemistry
Depositing User: Nikoleta Kiapidou
Date Deposited: 17 Feb 2016 13:47
Last Modified: 03 Jul 2019 00:48

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Project NameSussex Project NumberFunderFunder Ref
Deciphering the complex mechanisms that reprogram gene expression during Epstein Barr Virus replicatG0803MRCMR/J001708/1