Cam Hugh P, Sugiyama Tomoyasu, Chen Ee Sin, Chen Xi, FitzGerald Peter C, Grewal Shiv I S
Laboratory of Molecular Cell Biology, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Nat Genet. 2005 Aug;37(8):809-19. doi: 10.1038/ng1602. Epub 2005 Jun 24.
The organization of eukaryotic genomes into distinct structural and functional domains is important for the regulation and transduction of genetic information. Here, we investigated heterochromatin and euchromatin profiles of the entire fission yeast genome and explored the role of RNA interference (RNAi) in genome organization. Histone H3 methylated at Lys4, which defines euchromatin, was not only distributed across most of the chromosomal landscape but was also present at the centromere core, the site of kinetochore assembly. In contrast, histone H3 methylated at Lys9 and its interacting protein Swi6/HP1, which define heterochromatin, coated extended domains associated with a variety of repeat elements and small islands corresponding to meiotic genes. Notably, RNAi components were distributed throughout all these heterochromatin domains, and their localization depended on Clr4/Suv39h histone methyltransferase. Sequencing of small interfering RNAs (siRNAs) associated with the RITS RNAi effector complex identified hot spots of siRNAs, which mapped to a diverse array of elements in these RNAi-heterochromatin domains. We found that Clr4/Suv39h predominantly silenced repeat elements whose derived transcripts, transcribed mainly by RNA polymerase II, serve as a source for siRNAs. Our analyses also uncover an important role for the RNAi machinery in maintaining genomic integrity.
真核生物基因组组织成不同的结构和功能域对于遗传信息的调控和转导至关重要。在此，我们研究了整个裂殖酵母基因组的异染色质和常染色质图谱，并探讨了RNA干扰（RNAi）在基因组组织中的作用。在赖氨酸4处甲基化的组蛋白H3定义了常染色质，它不仅分布在大部分染色体区域，还存在于着丝粒核心，即动粒组装的位点。相比之下，在赖氨酸9处甲基化的组蛋白H3及其相互作用蛋白Swi6/HP1定义了异染色质，它们覆盖了与各种重复元件和对应于减数分裂基因的小岛屿相关的延伸区域。值得注意的是，RNAi组分分布在所有这些异染色质区域，其定位依赖于Clr4/Suv39h组蛋白甲基转移酶。与RITS RNAi效应复合物相关的小干扰RNA（siRNA）测序确定了siRNA热点，这些热点映射到这些RNAi - 异染色质区域中的各种元件。我们发现Clr4/Suv39h主要沉默那些其衍生转录本主要由RNA聚合酶II转录并作为siRNA来源的重复元件。我们的分析还揭示了RNAi机制在维持基因组完整性方面的重要作用。
