Nature:DNA复制与组蛋白甲基化之间的一个分子关联

2011-07-15 09:22 · pobee

DNA复制能破坏异染色质和常染色质的结构,但染色质中的组蛋白标记仍然能从一代准确传递到另一代。

背景:DNA复制能破坏异染色质和常染色质的结构,但染色质中的组蛋白标记仍然能从一代准确传递到另一代。

结论1:Li等人介绍了DNA复制与组蛋白甲基化之间的一个分子联系,这一线索提供了基因之外的标记在细胞周期中是怎样传递的。在裂殖酵母中,组蛋白H3K9的甲基化由细胞周期调控,RNA干涉参与这一调控。

结论2:2个沉默因子(Dos2 和 Rik1)组成的复合物,连同转录调控因子Mms19和DNA聚合酶-ε的催化亚基,在DNA复制及异染色质组装过程中是必需的,并影响异染色质内RNA聚合酶-II的活性。

发现这一分子关联的实验菌种——裂殖酵母

发现这一分子关联的实验菌种——裂殖酵母

生物探索推荐英文摘要

Coordination of DNA replication and histone modification by the Rik1–Dos2 complex

Abstract:Histone modification marks have an important role in many chromatin processes1, 2. During DNA replication, both heterochromatin and euchromatin are disrupted ahead of the replication fork and are then reassembled into their original epigenetic states behind the fork3, 4. How histone marks are accurately inherited from generation to generation is still poorly understood. In fission yeast (Schizosaccharomyces pombe), RNA interference (RNAi)-mediated histone methylation is cell cycle regulated. Centromeric repeats are transiently transcribed in the S phase of the cell cycle and are processed into short interfering RNAs (siRNAs) by the complexes RITS (RNA-induced initiation of transcriptional gene silencing) and RDRC (RNA-directed RNA polymerase complex)5, 6, 7. The small RNAs together with silencing factors—including Dos1 (also known as Clr8 and Raf1), Dos2 (also known as Clr7 and Raf2), Rik1 and Lid2—promote heterochromatic methylation of histone H3 at lysine 9 (H3K9) by a histone methyltransferase, Clr4 (refs 8–13). The methylation of H3K9 provides a binding site for Swi6, a structural and functional homologue of metazoan heterochromatin protein 1 (HP1)14. Here we characterize a silencing complex in fission yeast that contains Dos2, Rik1, Mms19 and Cdc20 (the catalytic subunit of DNA polymerase-ε). This complex regulates RNA polymerase II (RNA Pol II) activity in heterochromatin and is required for DNA replication and heterochromatin assembly. Our findings provide a molecular link between DNA replication and histone methylation, shedding light on how epigenetic marks are transmitted during each cell cycle.

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