Benetti Roberta, Gonzalo Susana, Jaco Isabel, Schotta Gunnar, Klatt Peter, Jenuwein Thomas, Blasco María A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain.
J Cell Biol. 2007 Sep 10;178(6):925-36. doi: 10.1083/jcb.200703081.
Mammalian telomeres have heterochromatic features, including trimethylated histone H3 at lysine 9 (H3K9me3) and trimethylated histone H4 at lysine 20 (H4K20me3). In addition, subtelomeric DNA is hypermethylated. The enzymatic activities responsible for these modifications at telomeres are beginning to be characterized. In particular, H4K20me3 at telomeres could be catalyzed by the novel Suv4-20h1 and Suv4-20h2 histone methyltransferases (HMTases). In this study, we demonstrate that the Suv4-20h enzymes are responsible for this histone modification at telomeres. Cells deficient for Suv4-20h2 or for both Suv4-20h1 and Suv4-20h2 show decreased levels of H4K20me3 at telomeres and subtelomeres in the absence of changes in H3K9me3. These epigenetic alterations are accompanied by telomere elongation, indicating a role for Suv4-20h HMTases in telomere length control. Finally, cells lacking either the Suv4-20h or Suv39h HMTases show increased frequencies of telomere recombination in the absence of changes in subtelomeric DNA methylation. These results demonstrate the importance of chromatin architecture in the maintenance of telomere length homeostasis and reveal a novel role for histone lysine methylation in controlling telomere recombination.
哺乳动物的端粒具有异染色质特征，包括赖氨酸9处三甲基化的组蛋白H3（H3K9me3）和赖氨酸20处三甲基化的组蛋白H4（H4K20me3）。此外，亚端粒DNA高度甲基化。负责端粒这些修饰的酶活性正开始被表征。特别是，端粒处的H4K20me3可由新型的Suv4-20h1和Suv4-20h2组蛋白甲基转移酶（HMTases）催化。在本研究中，我们证明Suv4-20h酶负责端粒处的这种组蛋白修饰。缺乏Suv4-20h2或同时缺乏Suv4-20h1和Suv4-20h2的细胞在端粒和亚端粒处的H4K20me3水平降低，而H3K9me3没有变化。这些表观遗传改变伴随着端粒延长，表明Suv4-20h HMTases在端粒长度控制中起作用。最后，缺乏Suv4-20h或Suv39h HMTases的细胞在亚端粒DNA甲基化没有变化的情况下，端粒重组频率增加。这些结果证明了染色质结构在维持端粒长度稳态中的重要性，并揭示了组蛋白赖氨酸甲基化在控制端粒重组中的新作用。
