Dr. Chi-Ju Chen, Assistant Professor
1991, B.S.¡@ Department of Plant Pathology, Entomology Division
¡@¡@¡@¡@¡@¡@ National Taiwan University, Taiwan
1997, Ph.D.¡@Genetics Program
¡@¡@¡@¡@¡@¡@ Michigan State University, USA
1997 - 2001¡@Post-doctoral Fellow
¡@¡@¡@¡@¡@¡@ The Wistar Institute, University of Pennsylvania, USA
2001 - 2002¡@Post-Doctoral Fellow (NHRI fellowship awarded)
¡@¡@¡@¡@¡@¡@ National Health Research Institute, Taiwan
¡@¡@¡@¡@¡@¡@ National Yang-Ming University, Taiwan
¡@¡@Epstein-Barr virus (EBV) is a human gamma herpesvirus associated with a number of malignancies, including nasopharyngeal carcinoma (NPC), Burkitt's lymphoma, T-cell lymphoma, gastric carcinoma, and Hodgkin's disease. EBV is transmitted orally, infects both mucosal epithelium and B-lymphocytes where it establishes a latent infection in B-lymphocytes. The EBV genome is maintained as a chromatin-like episome at latency. High levels of reactivation are thought to be a risk factor for several EBV-related malignant lymphoid cancers. However the role of EBV in human malignancy is complex and how the virus is reactivated is not well understood. The expression of immediate early gene, Zta, is a key step in the switch from latency to the lytic cycle of EBV. Zta binds to specific sequences, ZREs, found in viral lytic-cycle origin (OriLyt), as well as viral promoters of genes required for lytic DNA replication. Zta binding to its own promoter is thought to be a key step in the autostimulation of Zta transcription. It was shown that Zta binds to a cellular factor, CREB-binding protein (CBP), which processes acetyltransferase activity, and reactivation of latent EBV by Zta can be strongly stimulated by co-expression of CBP. Zta stimulates CBP acetyltransferase activity on nucleosomes.
¡@¡@A switch to expression of viral replication-associated genes can be achieved by treatment with histone deacetylase inhibitors, Tricostatin A (TSA) and sodium butyrate, suggesting the involvements of acetyltransferase activity in EBV reactivation. Zta interacts with CBP and stimulates its acetyltransferase activity. Our goal is to investigate the biological role of Zta-depend CBP acetyltransferase activity on Epstein-Barr virus (EBV) reactivation. Three specific aims are the recent interests:
1. Determine the effect of CBP on BZLF1 promoter and other Zta responsive viral genes upon reactivation.
2. Identify the HAT activity of CBP on oriLyt and how it affects EBV replication.
3. Determine the significance of acetylation modification of Zta by CBP.
1. Deng. Z., L. Lezina, C-J Chen, S. Shtivelband, W. So, and P. M. Lieberman. 2002. Telomeric proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication. Molecular Cell 9: 493-503.
2. Deng, Z.*, C-J Chen*, D. Zerby, H. Delecluse, P. M. Lieberman. 2001. Identification of acidic and aromatic residues in the Zta activation domain essential for Epstein-Barr virus reactivation. Journal of Virology 75: 10334-10347. (co-first authors).
3. Chen, Chi-Ju, Z. Deng,, A. Kim, G. Blobel, and P. M. Lieberman. 2000. Stimulation of nucleosome-directed histone acetylase activity of CBP by transcriptional activators. Molecular and Cellular Biology 21:476-487.
4. Zerby, D, C-J Chen, E. Poon, D. Lee, R. Shiekhattar, and P. M. Lieberman. 1999. The amino-terminal C/H1 domain of CREB binding protein mediates Zta transcriptional activation of latent Epstein-Barr virus. Molecular and Cellular Biology 19: 1617-1626.
5. Chen, Chi-Ju, M. E. Quentin, L. A. Brennan, C. Kukel, and S. M. Thiem. 1998. Lymantria dispar Nucleopolyhedrovirus hrf-1 expands the larval host range of Autographa californica nucleopolyhedrovirus. Journal of Virology 72: 2526-2531.
6. Chen, Chi-Ju and S. M. Thiem. 1997. Differential infectivity of two Autographa californica nucleopolyhedrovirus mutants on three permissive cell lines is the result of lef-7 deletion. Virology 227: 88-95.
7. Chen, Chi-Ju, D. J. Leisy, and S. M. Thiem. 1996. Physical map of Anagrapha falcifera nuclear polyhedrosis virus genome. Journal of General Virology 77: 167-171.
8. Chen, Chi-Ju*, Zhong Deng*, Jiaguang Chen, Michaela Chamberlin, Gerd Blobel, David Speicher and Paul M. Lieberman. 2003. The CBP bromodomain is required for activator stimulated nucleosome-specific acetyltransferase activity. In revision. (co-first authors).
Ph. D. Dissertation: Chen, Chi-Ju. 1997. Characterizations of baculovirus genes that influence infectivity in insect cell lines and larvae. Michigan State University
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