title: Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation.
abstract: 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.
authors.affiliation: Instituto de Biología Molecular de Barcelona, CID, Consejo Superior de Investigaciones Científicas, Parc Cientific de Barcelona, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Valls
authors.forename: Noemí
authors.initials: N
authors.lastname: Blanco-García
authors.forename: Naiara
authors.initials: N
authors.lastname: Aquizu
authors.forename: David
authors.initials: D
authors.lastname: Piedra
authors.forename: Conchi
authors.initials: C
authors.lastname: Estarás
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Cruz
authors.forename: Marian A
authors.initials: MA
authors.lastname: Martínez-Balbás
mesh_terms: 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
chemical_list: D000952:Antigens, Polyomavirus Transforming; D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; D050882:CREB-Binding Protein; D006655:Histone Deacetylases