Department of Biology, New York University, New York, NY, USA.
Epigenetics. 2012 Jan 1;7(1):14-9. doi: 10.4161/epi.7.1.18545.
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 ε 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.
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，染色质经历了一波破坏和重组。目前尚不清楚这些表观遗传标记是如何从上一代忠实地传递到下一代的。在裂殖酵母中，异染色质的标志是一种浓缩的染色质结构，即 H3K9 甲基化。这种保守的表观遗传标记是通过小干扰 RNA（siRNA）在细胞周期依赖性的方式介导的：在 S 期，异染色质被 RNA 聚合酶 II 短暂转录，随后转录物被加工成 siRNA。这些小 RNA 与其他关键沉默因子一起，包括 Dos1/Raf1/Clr8/Cmc1、Dos2/Raf2/Clr7/Cmc2 和 Rik1，通过组蛋白 H3K9 甲基转移酶 Clr4 介导 H3K9 甲基化。我们最近的发现表明，DNA 聚合酶 ε 亚基 Cdc20 与 Dos2-Rik1 复合物结合，对于 H3K9 甲基化和异染色质功能是必不可少的。此外，Cdc20 通过促进异染色质的 RNA 聚合酶 II 转录来调节 siRNA 的产生。这些数据表明，DNA 聚合酶成分可能通过协调 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控的 RNAi 依赖性异染色质沉默。我们提出了一个模型，即在 DNA 复制叉处，DNA 聚合酶亚基介导 RNAi 和组蛋白修饰所需的表观遗传因子的募集到异染色质，以促进组蛋白甲基化的忠实传递。
