Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation.
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.
Valls
Ester
E
Instituto de Biología Molecular de Barcelona, CID, Consejo Superior de Investigaciones Científicas, Parc Cientific de Barcelona, Barcelona, Spain.
Blanco-García
Noemí
N
Aquizu
Naiara
N
Piedra
David
D
Estarás
Conchi
C
de la Cruz
Xavier
X
Martínez-Balbás
Marian A
MA
D000107:Acetylation; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000037:antagonists & inhibitors*; D002843:Chromatin / Q000201:enzymology; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D000952:Antigens, Polyomavirus Transforming; D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; D050882:CREB-Binding Protein; D006655:Histone Deacetylases