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Deacetylase-independent function of SIRT6 couples GATA4 transcription factor and epigenetic activation against cardiomyocyte apoptosis.
Peng, Linyuan; Qian, Minxian; Liu, Zuojun; Tang, Xiaolong; Sun, Jie; Jiang, Yue; Sun, Shimin; Cao, Xinyue; Pang, Qiuxiang; Liu, Baohua.
Afiliación
  • Peng L; Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen 518055, China.
  • Qian M; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China.
  • Liu Z; Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen 518055, China.
  • Tang X; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China.
  • Sun J; Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen 518055, China.
  • Jiang Y; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China.
  • Sun S; Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen 518055, China.
  • Cao X; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China.
  • Pang Q; Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen 518055, China.
  • Liu B; Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China.
Nucleic Acids Res ; 48(9): 4992-5005, 2020 05 21.
Article en En | MEDLINE | ID: mdl-32239217
SIRT6 deacetylase activity improves stress resistance via gene silencing and genome maintenance. Here, we reveal a deacetylase-independent function of SIRT6, which promotes anti-apoptotic gene expression via the transcription factor GATA4. SIRT6 recruits TIP60 acetyltransferase to acetylate GATA4 at K328/330, thus enhancing its chromatin binding capacity. In turn, GATA4 inhibits the deacetylase activity of SIRT6, thus ensuring the local chromatin accessibility via TIP60-promoted H3K9 acetylation. Significantly, the treatment of doxorubicin (DOX), an anti-cancer chemotherapeutic, impairs the SIRT6-TIP60-GATA4 trimeric complex, blocking GATA4 acetylation and causing cardiomyocyte apoptosis. While GATA4 hyperacetylation-mimic retains the protective effect against DOX, the hypoacetylation-mimic loses such ability. Thus, the data reveal a novel SIRT6-TIP60-GATA4 axis, which promotes the anti-apoptotic pathway to prevent DOX toxicity. Targeting the trimeric complex constitutes a new strategy to improve the safety of DOX chemotherapy in clinical application.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Miocitos Cardíacos / Sirtuinas / Epigénesis Genética / Factor de Transcripción GATA4 / Antibióticos Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Miocitos Cardíacos / Sirtuinas / Epigénesis Genética / Factor de Transcripción GATA4 / Antibióticos Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido