TY - JOUR
T1 - MCAF1 and synergistic activation of the transcription of Epstein-Barr virus lytic genes by Rta and Zta
AU - Chang, Li Kwan
AU - Chuang, Jian Ying
AU - Nakao, Mitsuyoshi
AU - Liu, Shih Tung
N1 - Funding Information:
The National Health Research Institute of the Republic of China, Taiwan (Contract no. NHRI-EX98-9503BC); the National Science Council of the Republic of China, Taiwan (Contract no. NSC98-3112-B-182-005); and Chang-Gung Memorial Hospital (Contract no. CMRP-D160113). Funding for open access charge: National Science Council of the Republic of China, Taiwan.
PY - 2010/4/10
Y1 - 2010/4/10
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkq243
DO - 10.1093/nar/gkq243
M3 - Article
C2 - 20385599
AN - SCOPUS:77955794374
SN - 0305-1048
VL - 38
SP - 4687
EP - 4700
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 14
M1 - gkq243
ER -