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Journal of Virology, December 2003, p. 12841-12851, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12841-12851.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization of the Chromosomal Binding Sites and Dimerization Partners of the Viral Oncoprotein Meq in Marek's Disease Virus-Transformed T Cells

Alon M. Levy,1,2 Yoshihiro Izumiya,1,2 Peter Brunovskis,1,2 Liang Xia,1,2 Mark S. Parcells,3 Sanjay M. Reddy,4 Lucy Lee,4 Hong-Wu Chen,1,2 and Hsing-Jien Kung1,2*

Departmentof Biological Chemistry, School of Medicine, University of California, Davis, Davis, California 95616,1 UC Davis Cancer Center, Sacramento, California 95817,2 Center of Excellence for Poultry Science, Department of Poultry Science, University of Arkansas, Fayetteville, Arkansas 72701,3 Avian Disease and Oncology Laboratory, USDA-ARS, East Lansing, Michigan 488234

Received 18 June 2003/ Accepted 11 August 2003

Marek's disease virus (MDV) is an acute transforming alphaherpesvirus that causes T-cell lymphomas in chickens. We previously reported the identification of a putative oncogene, meq, that is encoded only by the oncogenic serotype of MDV. The gene product, Meq, is a latent protein that is consistently expressed in MDV-transformed lymphoblastoid cells and tumor cells. Meq has a bZIP (basic leucine zipper) structure resembling the family of Jun/Fos. The mechanism whereby Meq transforms T cells remains poorly understood. In this study, we explored the properties of Meq as a transcriptional factor. We analyzed Meq's dimerization partners and its target genes in MSB-1, an MDV-transformed T-cell line. By using in vitro assays, we first demonstrated Meq's potential to dimerize with a variety of bZIP proteins. We then identified c-Jun as the primary dimerization partner of Meq. Both are found to be colocalized in the nucleus and corecruited to promoters with AP-1 sequences. By using chromatin immunoprecipitation (ChIP), we scanned the entire MDV genome for Meq binding sites and found three regions that were enriched with Meq binding: the MDV lytic replication origin, the promoter for Meq, and the promoter for ICP4. Transactivation assays using the above promoters showed that Meq/Meq homodimers exhibited repression activity, whereas Meq/Jun heterodimers showed activation. Finally, we were able to show by ChIP that Meq is recruited to the interleukin-2 promoter in a region encompassing an AP-1 site. Thus, in addition to providing general knowledge about the transcriptional properties of Meq, our studies revealed for the first time the ability of Meq to interact with the latent MDV and host genomes. Our data suggest, therefore, a role for Meq in viral genome regulation during latency, in addition to its putative causal role in T-cell transformation.

* Corresponding author. Mailing address: UC Davis Cancer Center, Research Building III, Room 2400B, 4645 2nd Ave., Sacramento, CA 95817. Phone: (916) 734-1538. Fax: (916) 734-2589. E-mail: hkung{at}ucdavis.edu.

Journal of Virology, December 2003, p. 12841-12851, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12841-12851.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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