通过调节左节点信号来控制TET介导的DNA脱甲基化
Hai-Qiang Dai1,2, Bang-An Wang1,2, Lu Yang3,4
1State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Nature
|October 28, 2016
概括
通过破坏DNA甲基化和脱甲基化,导致小鼠10-11转位 (TET) 基因失活,从而影响早期胚胎发生过程中的节点信号传递.
科学领域:
- 表观遗传学和发育生物学
- 哺乳动物胚胎形成
- DNA甲基化动力学
背景情况:
- 哺乳动物的基因组具有表观遗传修饰,例如DNA甲基转移酶 (DNMT) 的细胞酶甲基化.
- 通过十一转位 (TET) 二氧化酶对5-甲基细胞酸的氧化介导脱甲基化.
- 在小鼠胚胎发生过程中,DNA甲基化和脱甲基化的确切作用需要进一步阐明.
研究的目的:
- 研究TET介导的DNA脱甲基化在小鼠胚胎生成中的功能意义.
- 阐明将DNA甲基化动态与胚胎信号通路联系起来的分子机制.
主要方法:
- 产生和分析具有非活化的Tet基因 (Tet无突变) 的小鼠.
- 胚胎表型的评估,包括化和中皮发育.
- 诺达尔,莱弗蒂和DNA甲基转移酶 (DNMT) 基因表达和甲基化模式的分子分析
主要成果:
- 的无活化导致胃化缺陷,原始纹状异常和中皮成熟障碍.
- 这些表型模仿了带有增强的节点信号的胚胎,由节点突变部分挽救.
- 缺乏导致左边基因表达减少,与DNA甲基化升高有关;破坏DNMT3A/3B挽救了这些缺陷.
结论:
- 在胚胎发育过程中,对5-甲基细胞因的TET介导氧化对于调节左节点信号至关重要.
- 通过TET和DNMT平衡的动态DNA甲基化和脱甲基化对于早期的身体计划形成至关重要.
- 这种表观遗传平衡的破坏会通过改变关键信号通路导致发育异常.
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