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Molecular and Cellular Biology, March 2003, p. 2055-2067, Vol. 23, No. 6
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.6.2055-2067.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Principal Role of TRAP/Mediator and SWI/SNF Complexes in Kaposi's Sarcoma-Associated Herpesvirus RTA-Mediated Lytic Reactivation

Yousang Gwack,1 Hwa Jin Baek,2 Hiroyuki Nakamura,1 Sun Hwa Lee,1 Michael Meisterernst,3 Robert G. Roeder,2 and Jae U. Jung1*

Tumor Virology Division, New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102,1 Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021,2 Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Munich, Germany3

Received 6 November 2002/ Returned for modification 10 December 2002/ Accepted 18 December 2002

An important step in the herpesvirus life cycle is the switch from latency to lytic reactivation. The RTA transcription activator of Kaposi's sarcoma-associated herpesvirus (KSHV) acts as a molecular switch for lytic reactivation. Here we demonstrate that KSHV RTA recruits CBP, the SWI/SNF chromatin remodeling complex, and the TRAP/Mediator coactivator into viral promoters through interactions with a short acidic sequence in the carboxyl region and that this recruitment is essential for RTA-dependent viral gene expression. The Brg1 subunit of SWI/SNF and the TRAP230 subunit of TRAP/Mediator were shown to interact directly with RTA. Consequently, genetic ablation of these interactions abolished KSHV lytic replication. These results demonstrate that the recruitment of CBP, SWI/SNF, and TRAP/Mediator complexes by RTA is the principal mechanism to direct well-controlled viral gene expression and thereby viral lytic reactivation.

* Corresponding author. Mailing address: Tumor Virology Division, New England Regional Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 786-1416. E-mail: jae_jung{at}hms.harvard.edu.

Molecular and Cellular Biology, March 2003, p. 2055-2067, Vol. 23, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.6.2055-2067.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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