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

Authors:
Mahmoudi T, Parra M, Vries RG, Kauder SE, Verrijzer CP, Ott M, Verdin E
In:
Source: J Biol Chem
Publication Date: (2006)
Issue: 281(29): 19960-8
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Jurkat
Species: human
Tissue Origin: blood
Jurkat-modified
Species: human
Tissue Origin:
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
Tat is a critical viral transactivator essential for HIV gene expression. Activation involves binding to an RNA stem-loop structure and recruitment of the pTEFb elongation factor. 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, suppresses Tat-mediated transactivation. Cells lacking INI-1 (G401, MON) or BRG-1 (C33A) exhibit defective transactivation by Tat that is restored upon INI-1 and BRG-1 expression, respectively. Tat is coimmunoprecipitated with several SWI/SNF subunits, including INI-1, BRG-1 and b-actin. Importantly, the SWI/SNF complex interacts with the integrated HIV promoter in a Tat-dependent manner. We also find that INI-1 and BRG-1 synergize with the p300 acetyltransferase to activate the HIV promoter. This synergism depends on the acetyltransferase activity of p300 and on Tat lysines 50 and 51. In conclusion, Tat-mediated activation of the HIV promoter requires the SWI/SNF complex in synergy with the coactivator p300.