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Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding.
J Gen Virol. 2016 Mar; 97(3):725-732.JG

Abstract

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 downregulation of MHC class II gene expression via the targeted repression of CIITA, the cellular master regulator of MHC class II gene expression. This 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.

Authors+Show Affiliations

School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26653871

Citation

Balan, Nicolae, et al. "Repression of CIITA By the Epstein-Barr Virus Transcription Factor Zta Is Independent of Its Dimerization and DNA Binding." The Journal of General Virology, vol. 97, no. 3, 2016, pp. 725-732.
Balan N, Osborn K, Sinclair AJ. Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding. J Gen Virol. 2016;97(3):725-732.
Balan, N., Osborn, K., & Sinclair, A. J. (2016). Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding. The Journal of General Virology, 97(3), 725-732. https://doi.org/10.1099/jgv.0.000369
Balan N, Osborn K, Sinclair AJ. Repression of CIITA By the Epstein-Barr Virus Transcription Factor Zta Is Independent of Its Dimerization and DNA Binding. J Gen Virol. 2016;97(3):725-732. PubMed PMID: 26653871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding. AU - Balan,Nicolae, AU - Osborn,Kay, AU - Sinclair,Alison J, Y1 - 2015/12/11/ PY - 2015/12/15/entrez PY - 2015/12/15/pubmed PY - 2016/7/28/medline SP - 725 EP - 732 JF - The Journal of general virology JO - J. Gen. Virol. VL - 97 IS - 3 N2 - 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 downregulation of MHC class II gene expression via the targeted repression of CIITA, the cellular master regulator of MHC class II gene expression. This 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. SN - 1465-2099 UR - https://www.unboundmedicine.com/medline/citation/26653871/Repression_of_CIITA_by_the_Epstein_Barr_virus_transcription_factor_Zta_is_independent_of_its_dimerization_and_DNA_binding_ L2 - http://jgv.microbiologyresearch.org/pubmed/content/journal/jgv/10.1099/jgv.0.000369 DB - PRIME DP - Unbound Medicine ER -