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J. Biol. Chem., Vol. 281, Issue 29, 19960-19968, July 21, 2006

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The SWI/SNF Chromatin-remodeling Complex Is a Cofactor for Tat Transactivation of the HIV Promoter^*

Tokameh Mahmoudi, Maribel Parra, Robert G. J. Vries, Steven E. Kauder, C. Peter Verrijzer, Melanie Ott, and Eric Verdin¹

From the Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158 and the Department of Biochemistry, Centre for Biomedical Genetics, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands

Tat is a critical viral transactivator essential for human immunodeficiency virus (HIV) gene expression. Activation involves binding to an RNA stem-loop structure and recruitment of the positive transcription elongation factor b. Tat also induces the remodeling of a single nucleosome in the HIV promoter. However, the mechanism of this remodeling has remained unclear. Knockdown of INI-1 and BRG-1, two components of the SWI/SNF chromatin-remodeling complex, suppressed Tat-mediated transactivation. Cells lacking INI-1 (G401 and MON) or BRG-1 (C33A) exhibited defective transactivation by Tat that was restored upon INI-1 and BRG-1 expression, respectively. Tat was co-immunoprecipitated with several SWI/SNF subunits, including INI-1, BRG-1, and -actin. The SWI/SNF complex interacted with the integrated HIV promoter in a Tat-dependent manner. We also found that INI-1 and BRG-1 synergized with the p300 acetyltransferase to activate the HIV promoter. This synergism depended on the acetyltransferase activity of p300 and on Tat Lys⁵⁰ and Lys⁵¹. In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300.

Received for publication, April 7, 2006 , and in revised form, May 8, 2006.

^* This work was supported in part by the National Institutes of Health Grants PO1 A158708 and RO1 GM051671 and by the J. David Gladstone Institutes. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Gladstone Inst. of Virology and Immunology, 1650 Owens St., San Francisco, CA 94158. Tel.: 415-734-4808; Fax: 415-355-0855; E-mail: everdin{at}gladstone.ucsf.edu.

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