PMID: 9159154May 27, 1997Paper

Reactivation of silenced, virally transduced genes by inhibitors of histone deacetylase

Proceedings of the National Academy of Sciences of the United States of America
W Y ChenT M Townes

Abstract

Retroviral and adeno-associated viral sequences can dramatically silence transgene expression in mice. We now report that this repression also occurs in stably infected HeLa cells when the cells are grown without selection. Expression of a transduced lacZ gene (rAAV/CMVlacZ) is silenced in greater than 90% of cells after 60 days in culture. Surprisingly, high-level expression can be reactivated by treating the cells with sodium butyrate or trichostatin A but not with 5-azacytidine. When cell clones with integrated copies of rAAV/CMVlacZ were isolated, lacZ expression was silenced in 80% of the clones; however, lacZ expression was reactivated in all of the silenced clones by treatment with butyrate or trichostatin A. The two drugs also reactivated a silenced globin gene construct (rAAV/HS2alphabetaAS3) in stably infected K562 cells. Trichostatin A is a specific inhibitor of histone deacetylase; therefore, we propose that hyperacetylation of histones after drug treatment changes the structure of chromatin on integrated viral sequences and relieves repression of transduced genes. The reactivation of silenced, transduced genes has implications for gene therapy. Efficient viral gene transfer followed by drug treatment to relieve sup...Continue Reading

References

Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C E WalshR J Samulski
Feb 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·T D PalmerA D Miller
Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J J CaterinaT M Townes
Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R M KotinK I Berns
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D Y TuanD P Lee
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·P T CurtinY W Kan
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T M RyanR L Brinster
Mar 19, 1982·Molecular and Cellular Biochemistry·H Maeno
Feb 5, 1982·Molecular and Cellular Biochemistry·J Kruh
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·J L MillerA W Nienhuis
Aug 1, 1995·Proceedings of the National Academy of Sciences of the United States of America·K YoshiuraS Hirohashi
Jan 14, 1993·The New England Journal of Medicine·S P PerrineN F Olivieri
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·D W RussellA D Miller
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·S L McCuneT M Townes
Oct 25, 1994·Nucleic Acids Research·S L McCune, T M Townes
Apr 19, 1996·Science·A P Wolffe
Dec 19, 1996·Nature·A J Bannister, T Kouzarides

❮ Previous
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Citations

Dec 11, 1999·Developmental Dynamics : an Official Publication of the American Association of Anatomists·K BlaveriJ E Morgan
Dec 18, 2001·Genes, Chromosomes & Cancer·M W McBurneyB Davies
Aug 19, 2010·Cell Stress & Chaperones·Frank BoschelliKim T Arndt
Apr 25, 2012·Biochemical and Biophysical Research Communications·Chang Sik ParkDo Han Kim
Feb 15, 2005·Clinics in Dermatology·Ulrich R Hengge
Jan 20, 2004·Gene·Alessandro MarcelloMauro Giacca
Oct 6, 2000·Phytochemistry·J P MurphyW A Tramontano
Sep 2, 1999·Advances in Enzyme Regulation·D KepplerA Nies
Oct 31, 1998·Brain Research. Molecular Brain Research·A SalminenT Suuronen
May 29, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Andrea BartoliPierfrancesco Marconi
Nov 5, 2002·Methods : a Companion to Methods in Enzymology·Jean-Charles Paterna, Hansruedi Büeler
Jul 24, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Akihiro OtsukiYoshinaga Saeki
Jun 30, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jennifer B NietupskiRonald K Scheule
Jul 13, 2011·Nature Biotechnology·Fabien PalazzoliFlorence Bonnin-Rouleux
Aug 23, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Valérie BergoglioThierry Magnaldo
Jun 9, 1999·The Biochemical Journal·G JedlitschkyB Burchell
Nov 3, 2001·Molecular Urology·Y Kaneda
Jan 25, 2000·Journal of Hematotherapy & Stem Cell Research·N Dalyot-HermanA Oppenheim
May 5, 2007·Assay and Drug Development Technologies·Jennifer JonesOlaf Kutsch
May 13, 2008·Assay and Drug Development Technologies·Adam B WeinglassMaria L Garcia
Oct 3, 2006·Cloning and Stem Cells·Stacey GoicoaJuan Domínguez-Bendala
May 15, 2003·Molecular Plant-microbe Interactions : MPMI·Mark SeemanpillaiAli Rezaian
May 22, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peizhou JiangShu-Hui Yen
Jun 6, 2008·Journal of Virology·Magalie Penaud-BudlooRichard O Snyder

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