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论文题目: The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy
英文论文题目: The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy
第一作者: Wang, ZH; Zhang, XJ; Ji, YX; Zhang, P; Deng, KQ; Gong, J; Ren, SX; Wang, XH; Chen, I; Wang, H; Gao, C; Yokota, T; Ang, YS; Li, S; Cass, A; Vondriska, TM; Li, GP; Deb, A; Srivastava, D; Yang, HT; Xiao, XS; Li, HL; Wang, YB
英文第一作者: Wang, ZH; Zhang, XJ; Ji, YX; Zhang, P; Deng, KQ; Gong, J; Ren, SX; Wang, XH; Chen, I; Wang, H; Gao, C; Yokota, T; Ang, YS; Li, S; Cass, A; Vondriska, TM; Li, GP; Deb, A; Srivastava, D; Yang, HT; Xiao, XS; Li, HL; Wang, YB
联系作者: Li, HL (reprint author), Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan, Peoples R China.
英文联系作者: Li, HL (reprint author), Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan, Peoples R China.
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发表年度: 2016
卷: 22
期: 10
页码: 1131-1139
摘要: Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we identified a heart-enriched long noncoding (Inc)RNA, named cardiac-hypertrophy-associated epigenetic regulator (Chaer), which is necessary for the development of cardiac hypertrophy. Mechanistically, Chaer directly interacts with the catalytic subunit of polycomb repressor complex 2 (PRC2). This interaction, which is mediated by a 66-mer motif in Chaer, interferes with PRC2 targeting to genomic loci, thereby inhibiting histone H3 lysine 27 methylation at the promoter regions of genes involved in cardiac hypertrophy. The interaction between Chaer and PRC2 is transiently induced after hormone or stress stimulation in a process involving mammalian target of rapamycin complex 1, and this interaction is a prerequisite for epigenetic reprogramming and induction of genes involved in hypertrophy. Inhibition of Chaer expression in the heart before, but not after, the onset of pressure overload substantially attenuates cardiac hypertrophy and dysfunction. Our study reveals that stress-induced pathological gene activation in the heart requires a previously uncharacterized IncRNA-dependent epigenetic checkpoint.
英文摘要: Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we identified a heart-enriched long noncoding (Inc)RNA, named cardiac-hypertrophy-associated epigenetic regulator (Chaer), which is necessary for the development of cardiac hypertrophy. Mechanistically, Chaer directly interacts with the catalytic subunit of polycomb repressor complex 2 (PRC2). This interaction, which is mediated by a 66-mer motif in Chaer, interferes with PRC2 targeting to genomic loci, thereby inhibiting histone H3 lysine 27 methylation at the promoter regions of genes involved in cardiac hypertrophy. The interaction between Chaer and PRC2 is transiently induced after hormone or stress stimulation in a process involving mammalian target of rapamycin complex 1, and this interaction is a prerequisite for epigenetic reprogramming and induction of genes involved in hypertrophy. Inhibition of Chaer expression in the heart before, but not after, the onset of pressure overload substantially attenuates cardiac hypertrophy and dysfunction. Our study reveals that stress-induced pathological gene activation in the heart requires a previously uncharacterized IncRNA-dependent epigenetic checkpoint.
刊物名称: NATURE MEDICINE
英文刊物名称: NATURE MEDICINE
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学科: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
英文学科: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
影响因子: 29.886
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论文类别: Article
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