维护 Uhrf1 依存的 H3K23 无处不在对,维护 DNA 甲基化和复制
Atsuya Nishiyama1, Luna Yamaguchi, Jafar Sharif
1Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan. anishiya@med.nagoya-cu.ac.jp
Nature
|September 10, 2013
概括
在复制过程中维护DNA甲基化过程中,Uhrf1依赖的基因素H3无处不在是必不可少的. 这项研究揭示了DNA甲基化和DNA复制通过基因素H3无处不在化之间的机械联系.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 在DNA复制过程中,忠实的DNA甲基化模式传播对于稳定的细胞表型至关重要.
- Uhrf1 (具有PHD和戒指域1的ubiquitin-like) 通过其SRA域结合半甲基化DNA,并通过Dnmt1进行甲基化维护.
- 连接Uhrf1,DNA甲基化维护和DNA复制的精确机制在很大程度上仍未被阐明.
研究的目的:
- 调查Uhrf1在协调DNA甲基化维护与DNA复制中的作用.
- 阐明基因组修饰和复制过程中的DNA甲基化维护之间的机械联系.
主要方法:
- 利用Xenopus蛋提取物建立一个体外系统来研究维护DNA甲基化.
- 研究了 Dnmt1 枯竭对 Uhrf1 依赖性 histone H3 无处不在的影响.
- 在体外检查了Dnmt1和无处不在的基因组H3之间的相互作用.
- 评估了哺乳动物培养细胞中Uhrf1的RING手指突变体在Dnmt1招募和DNA甲基化维护方面的功能.
主要成果:
- 证明了Uhrf1依赖的基因素H3无处不在是维护DNA甲基化的一个先决条件.
- 在Dnmt1耗尽后,观察到Uhrf1依赖的基因素H3在lysine 23的无处不在积累.
- 表明Dnmt1优先与无处不在的H3.3相关联.
- 发现Uhrf1的RING指突变损害了Dnmt1对复制部位的招募和细胞中DNA甲基化维护.
结论:
- 确立了Uhrf1依赖的基因组H3无处不在作为DNA复制过程中维护DNA甲基化的关键因素.
- 提供了第一个机械证据,将DNA甲基化和DNA复制通过基因素H3无处不在化联系起来.
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