Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin
Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin
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DOI：
10.1038/nsmb.1406
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发表时间：
2008-04-01
影响因子：
16.8
通讯作者：
Grewal, Shiv I. S.
中科院分区：
文献类型：
--
作者：
Zhang, Ke;Mosch, Kerstin;Grewal, Shiv I. S.
异染色质组装，包括组蛋白H3赖氨酸9 （H3K9me）的甲基化，调节各种染色体过程。在裂变酵母中，异染色质以rnai依赖的方式靶向特定重复位点，在扩展的结构域中扩散，从而发挥区域表观遗传控制作用。Clr4甲基转移酶复合物（ClrC）负责异染色质的成核和扩散；然而，它对异染色质重复序列的招募却知之甚少。在这里，我们证明了ClrC成分分布在整个异色域。为了使异染色质成核，含有ClrC亚基的WD结构域Rik1通过RNAi机制（包括rna诱导转录沉默（RITS）复合体）加载到转录的重复序列上。此外，我们发现Clr4的色域特异性地结合H3K9me，这是异染色质扩散所必需的。我们的分析描述了异染色质结构域组装的顺序步骤，并表明Clr4“写”和“读”H3K9me的能力有助于通过连续的细胞分裂维持异染色质。
Heterochromatin assembly, involving methylation of histone H3 lysine 9 (H3K9me), regulates various chromosomal processes. In fission yeast, heterochromatin targeted to specific repeat loci in an RNAi-dependent manner spreads across extended domains to exert regional epigenetic control. The Clr4 methyltransferase complex (ClrC) is responsible for nucleation and spreading of heterochromatin; however, its recruitment to heterochromatic repeats is poorly understood. Here we demonstrate that ClrC components are distributed throughout heterochromatic domains. To nucleate heterochromatin, Rik1, a WD domain containing subunit of ClrC, is loaded onto the transcribed repeats via RNAi machinery including the RNA-induced transcriptional silencing (RITS) complex. Furthermore, we show that the chromodomain of Clr4 binds specifically to H3K9me that is essential for the spreading of heterochromatin. Our analyses delineate sequential steps for the assembly of heterochromatic domains and suggest that the ability of Clr4 to both 'write' and 'read' H3K9me facilitates heterochromatin maintenance through successive cell divisions.