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Author Spotlight: RNAi Inheritance and ChIP in C. elegans
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通过RNAi和海斯H3K9甲基化合的表观遗传
Ruby Yu1, Xiaoyi Wang1, Danesh Moazed2
1Department of Cell Biology and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.
Nature
|June 22, 2018
概括
在裂变酵母中,基因沉默的表观遗传是通过涉及RNA干扰 (RNAi) 和基因组H3酸9甲基化 (H3K9me) 的合正反循环来维持的. 这种协同机制确保跨代表观遗传记忆独立于DNA序列.
科学领域:
- 表观遗传学
- 分子生物学
- 遗传学
背景情况:
- 基因组转化后修饰 (PTM) 建立了细胞类型特异性基因表达的表观遗传状态.
- 积极的反机制涉及识别和催化现有的基因组修饰的酶被认为可以维持这些状态.
- 之前的研究表明,仅基于PTM基因的基因反是不够的,如果没有额外的输入,就无法进行表观遗传.
研究的目的:
- 调查RNA干扰 (RNAi) 和基因组H3氨酸9甲基化 (H3K9me) 的正反循环是否可以独立于DNA序列保持表观遗传沉默.
- 要确定这种合反机制是否在未经突变的野生类型细胞中起作用.
- 阐明协同反在表观遗传和防除中的作用.
主要方法:
- 使用了裂变酵母Schizosaccharomyces pombe模型系统.
- 研究了siRNA诱导的H3K9me和无色基因的沉默.
- 分析了二次siRNA和H3K9me3的传播.
- 评估 RNAi 和 H3K9me 在保持沉默方面的需求.
- 研究了基因组脱甲基和基因间相互作用对静音稳定性的影响.
主要成果:
- 证明siRNA诱导的H3K9me和基因沉默可以在野性分裂酵母中的多个细胞分裂期间在cis中被表观遗传.
- 表明遗传涉及二次siRNA和H3K9me3向目标基因和周围区域的传播.
- 确认RNAi和H3K9me都需要用于保持沉默的协同作用.
- 观察到仅通过基因组PTM反维持的沉默是通过H3K9脱甲基化或基因间相互作用消除的.
结论:
- RNAi机制可以独立于DNA序列或启用突变来调解跨代表观遗传.
- siRNA和H3K9me正反循环的合有协同作用,以保持表观遗传沉默.
- 这种协同机制保护表观遗传基因不被删除,突显了它在表观遗传记忆中的重要性.
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