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论文题目: Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals
英文论文题目: Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals
第一作者: Zhao, Q; Zhang, JQ; Chen, RY; Wang, LN; Li, B; Cheng, H; Duan, XY; Zhu, HJ; Wei, W; Li, JW; Wu, QH; Han, JDJ; Yu, WQ; Gao, SR; Li, GH; Wong, JM
英文第一作者: Zhao, Q; Zhang, JQ; Chen, RY; Wang, LN; Li, B; Cheng, H; Duan, XY; Zhu, HJ; Wei, W; Li, JW; Wu, QH; Han, JDJ; Yu, WQ; Gao, SR; Li, GH; Wong, JM
联系作者: Wong, JM (reprint author), East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China.
英文联系作者: Wong, JM (reprint author), East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China.
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发表年度: 2016
卷: 7
期:
页码: 12464
摘要: In mammals it is unclear if UHRF1-mediated DNA maintenance methylation by DNMT1 is strictly dependent on histone H3K9 methylation. Here we have generated an Uhrf1 knockin (KI) mouse model that specifically abolishes the H3K9me2/3-binding activity of Uhrf1. The homozygous Uhrf1 KI mice are viable and fertile, and exhibit similar to 10% reduction of DNA methylation in various tissues. The reduced DNA methylation occurs globally in the genome and does not restrict only to the H3K9me2/3 enriched repetitive sequences. In vitro UHRF1 binds with higher affinity to reconstituted nucleosome with hemi-methylated CpGs than that with H3K9me2/3, although it binds cooperatively to nucleosome with both modifications. We also show that the nucleosome positioning affects the binding of methylated DNA by UHRF1. Thus, while our study supports a role for H3K9 methylation in promoting DNA methylation, it demonstrates for the first time that DNA maintenance methylation in mammals is largely independent of H3K9 methylation.
英文摘要: In mammals it is unclear if UHRF1-mediated DNA maintenance methylation by DNMT1 is strictly dependent on histone H3K9 methylation. Here we have generated an Uhrf1 knockin (KI) mouse model that specifically abolishes the H3K9me2/3-binding activity of Uhrf1. The homozygous Uhrf1 KI mice are viable and fertile, and exhibit similar to 10% reduction of DNA methylation in various tissues. The reduced DNA methylation occurs globally in the genome and does not restrict only to the H3K9me2/3 enriched repetitive sequences. In vitro UHRF1 binds with higher affinity to reconstituted nucleosome with hemi-methylated CpGs than that with H3K9me2/3, although it binds cooperatively to nucleosome with both modifications. We also show that the nucleosome positioning affects the binding of methylated DNA by UHRF1. Thus, while our study supports a role for H3K9 methylation in promoting DNA methylation, it demonstrates for the first time that DNA maintenance methylation in mammals is largely independent of H3K9 methylation.
刊物名称: NATURE COMMUNICATIONS
英文刊物名称: NATURE COMMUNICATIONS
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学科: Multidisciplinary Sciences
英文学科: Multidisciplinary Sciences
影响因子: 12.124
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论文类别: Article
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