DNA replication, RNAi and epigenetic inheritance.
DNA replication, RNAi and epigenetic inheritance.
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DOI：
10.4161/epi.7.1.18545
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发表时间：
2012-01-01
期刊：
影响因子：
3.7
通讯作者：
Li, Fei
中科院分区：
文献类型：
--
作者：
Gonzalez, Marlyn;Li, Fei
表观遗传标记，如组蛋白甲基化，在染色质结构和基因表达中起着核心作用。在DNA复制过程中，染色质经历了一波分裂和重组。人们对表观遗传标记如何从一代人忠实地遗传到下一代人知之甚少。在裂殖酵母中，异染色质（一种浓缩的染色质结构）的标志是H3 K9甲基化。这种保守的表观遗传标记由小干扰RNA（siRNA）以细胞周期依赖性方式介导：在S期，异染色质被RNAP II短暂转录，转录物随后被加工成siRNA。这些小RNA与其他关键沉默因子，包括Dos 1/Raf 1/Clr 8/Cmc 1、Dos 2/Raf 2/Clr 7/Cmc 2和Rik 1一起，通过组蛋白H3 K9甲基转移酶Clr 4介导H3 K9甲基化。我们最近的研究结果表明，DNA聚合酶，Cdc 20，与Dos 2-Rik 1复合物的α亚基，是必不可少的H3 K9甲基化和异染色质功能。此外，Cdc 20通过促进异染色质的RNAP II转录来调节siRNA的产生。这些数据表明，DNA聚合酶组分可能通过协调DNA复制、RNAi和组蛋白甲基化在组蛋白甲基化的遗传中发挥关键作用，并解释了先前观察到的细胞周期调节的RNAi依赖的异染色质沉默。我们提出了一个模型，其中，在DNA复制叉，DNA聚合酶亚基介导的招募所需的RNAi和组蛋白修饰异染色质的表观遗传因子，以促进组蛋白甲基化的忠实传输。
Epigenetic marks, such as histone methylation, play a central role in chromatin structure and gene expression. During DNA replication, chromatin undergoes a wave of disruption and reassembly. Little is known about how the epigenetic marks are faithfully inherited from one generation to the next. In fission yeast, the hallmark of heterochromatin, a condensed chromatin structure, is H3K9 methylation. This conserved epigenetic mark is mediated by small interference RNAs (siRNAs) in a cell cycle-dependent manner: at S phase, heterochromatin is briefly transcribed by RNAP II and the transcripts are subsequently processed into siRNAs. These small RNAs, together with other key silencing factors, including Dos1/Raf1/Clr8/Cmc1, Dos2/Raf2/Clr7/Cmc2 and Rik1, mediate H3K9 methylation by the histone H3K9 methyltransferase Clr4. Our recent findings indicate that the epsilon subunit of DNA polymerase, Cdc20, associates with the Dos2-Rik1 complex and is essential for H3K9 methylation and heterochromatin function. Moreover, Cdc20 regulates siRNA generation by promoting RNAP II transcription of heterochromatin. These data suggest that DNA polymerase components may play a key role in the inheritance of histone methylation by coordinating DNA replication, RNAi and histone methylation, and explain previously observed cell cycle-regulated RNAi-dependent heterochromatin silencing. We propose a model in which, at DNA replication forks, DNA polymerase subunits mediate the recruitment of epigenetic factors required for RNAi and histone modification to heterochromatin to promote the faithful transmission of histone methylation.