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Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation.

Valls E., Blanco-Garcia N., Aquizu N., Piedra D., Estaras C., de la Cruz X., Martinez-Balbas M.A.

Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This repression is concomitant with histone H3 deacetylation and is TSA sensitive. Moreover, our results demonstrate that T antigen interacts with HDAC1 in vitro in an Rb-independent manner. In addition, the overexpression of HDAC1 cooperates with T antigen to antagonize CBP transactivation function and correlates with chromatin deacetylation of the TK promoter. Finally, decreasing HDAC1 levels with small interfering RNA (siRNA) partially abolishes T antigen-induced repression. These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins.

Nucleic Acids Res. 35:1958-1968(2007) [PubMed] [Europe PMC]