Involvement of chromatin and histone deacetylation in SV40T antigen transcription regulation

Ester Valls, Noemí Blanco-García, Naiara Aquizu, David Piedra, Conchi Estarás, Xavier de la Cruz, Marian A. Martínez-Balbás

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)1958-1968
Number of pages11
JournalNucleic Acids Research
Volume35
Issue number6
DOIs
StatePublished - Mar 2007
Externally publishedYes

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