MCAF1 and synergistic activation of the transcription of Epstein-Barr virus lytic genes by Rta and Zta

Li Kwan Chang, Jian Ying Chuang, Mitsuyoshi Nakao, Shih Tung Liu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle. The two proteins often collaborate to activate the transcription of EBV lytic genes synergistically. This study demonstrates that Rta and Zta form a complex via an intermediary protein, MCAF1, on Zta response element (ZRE) in vitro. The interaction among these three proteins in P3HR1 cells is also verified via coimmunoprecipitation, CHIP analysis and confocal microscopy. The interaction between Rta and Zta in vitro depends on the region between amino acid 562 and 816 in MCAF1. In addition, overexpressing MCAF1 enhances and introducing MCAF1 siRNA into the cells markedly reduces the level of the synergistic activation in 293T cells. Moreover, the fact that the synergistic activation depends on ZRE but not on Rta response element (RRE) originates from the fact that Rta and Zta are capable of activating the BMRF1 promoter synergistically after an RRE but not ZREs in the promoter are mutated. The binding of Rta-MCAF1-Zta complex to ZRE but not RRE also explains why Rta and Zta do not use RRE to activate transcription synergistically. Importantly, this study elucidates the mechanism underlying synergistic activation, which is important to the lytic development of EBV.

Original languageEnglish
Article numbergkq243
Pages (from-to)4687-4700
Number of pages14
JournalNucleic Acids Research
Volume38
Issue number14
DOIs
Publication statusPublished - Apr 10 2010
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

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