title: The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter.
abstract: 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 beta-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 Lys(50) and Lys(51). In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300.
authors: Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA.
authors: Tokameh
authors: T
authors: Mahmoudi
authors: Maribel
authors: M
authors: Parra
authors: Robert G J
authors: RG
authors: Vries
authors: Steven E
authors: SE
authors: Kauder
authors: C Peter
authors: CP
authors: Verrijzer
authors: Melanie
authors: M
authors: Ott
authors: Eric
authors: E
authors: Verdin