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The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter

By T. (Tokameh) Mahmoudi, M. (Maribel) Parra, R.G.J. (Robert) Vries, S.E. (Steven) Kauder, C.P. (Peter) Verrijzer, M. (Melanie) Ott and E. (Eric) Verdin


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 β-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

Year: 2006
DOI identifier: 10.1074/jbc.M603336200
OAI identifier: oai:repub.eur.nl:70914
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