Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of active chromatin states in fission yeast
Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of active chromatin states in fission yeast
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DOI：
10.1073/pnas.182436399
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发表时间：
2002-12-10
影响因子：
11.1
通讯作者：
Grewal, SIS
中科院分区：
文献类型：
--
作者：
Noma, K;Grewal, SIS
已知组蛋白H3在赖氨酸4（H3 Lys-4）或赖氨酸9（H3 Lys-9）处的甲基化分别限定从裂殖酵母到人类的活性和沉默染色体结构域。然而，在芽殖酵母中，H3 Lys-4甲基化也是端粒和核糖体DNA沉默染色质组装所必需的。在这里，我们证明，删除set 1，它编码的蛋白质含有一个RNA识别基序在其氨基末端和一个SET结构域在羧基末端，废除H3的赖氨酸-4甲基化在裂殖酵母。与芽殖酵母不同，Set 1介导的H3 Lys-4甲基化在裂殖酵母的沉默交配型区域和着丝粒处的异染色质组装中是不需要的。我们的分析表明，H3 Lys-4甲基化是一种稳定的组蛋白修饰，存在于整个细胞周期，包括有丝分裂。set 1Delta细胞中H3 Lys-4甲基化的丧失与组蛋白H3乙酰化水平的降低相关，表明H3 Lys-4甲基化和H3尾部乙酰化之间存在机制联系。我们认为，甲基化的H3赖氨酸-4主要作用于转录平衡的常染色质结构域的维护，而这种修饰是在裂殖酵母，而不是利用H3赖氨酸-9甲基化的异染色质形成。
Methylation of histone H3 at lysine 4 (H3 Lys-4) or lysine 9 (H3 Lys-9) is known to define active and silent chromosomal domains respectively from fission yeast to humans. However, in budding yeast, H3 Lys-4 methylation is also necessary for silent chromatin assembly at telomeres and ribosomal DNA. Here we demonstrate that deletion of set1, which encodes a protein containing an RNA recognition motif at its amino terminus and a SET domain at the carboxy terminus, abolishes H3 Lys-4 methylation in fission yeast. Unlike in budding yeast, Set1-mediated H3 Lys-4 methylation is not required for heterochromatin assembly at the silent mating-type region and centromeres in fission yeast. Our analysis suggests that H3 Lys-4 methylation is a stable histone modification present throughout the cell cycle, including mitosis. The loss of H3 Lys-4 methylation in set1Delta cells is correlated with a decrease in histone H3 acetylation levels, suggesting a mechanistic link between H3 Lys-4 methylation and acetylation of the H3 tail. We suggest that methylation of H3 Lys-4 primarily acts in the maintenance of transcriptionally poised euchromatic domains, and that this modification is dispensable for heterochromatin formation in fission yeast, which instead utilizes H3 Lys-9 methylation.