Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast
Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast
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DOI：
10.1038/nature00883
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发表时间：
2002-07-04
期刊：
影响因子：
64.8
通讯作者：
Allis, CD
中科院分区：
文献类型：
--
作者：
Sun, ZW;Allis, CD
在真核生物中，基因组的DNA与组蛋白一起包装形成核小体丝，核小体丝反过来折叠成一系列不太清楚的染色质结构（1）。组蛋白尾部结构域的翻译后修饰调节染色质结构和基因表达（2-4）。其中，组蛋白泛素化的了解甚少。在这里，我们表明，泛素结合酶Rad 6（Ubc 2）介导的组蛋白H3在赖氨酸4（赖氨酸4）通过泛素化的H2 B在赖氨酸123在酵母（酿酒酵母）的甲基化。此外，H3（Lys 4）甲基化在H2 B-K123 R突变体中被消除，而H3-K4 R保留H2 B（Lys 123）泛素化。这些数据表明一个单向的调节途径，其中H2 B（赖氨酸123）的泛素化是H3（赖氨酸4）甲基化的先决条件。我们还表明，H2 B-K123 R突变扰乱沉默在端粒，提供Rad 6介导的H2 B（赖氨酸123）泛素化，Set 1介导的H3（赖氨酸4）甲基化和转录沉默之间的功能联系。因此，这些数据揭示了一种通过在不同的组蛋白尾部进行协调的组蛋白修饰来进行基因调控的途径。我们称之为组蛋白修饰的“反尾”调节，这是对组蛋白密码假说的一种预测（5，6）
In eukaryotes, the DNA of the genome is packaged with histone proteins to form nucleosomal filaments, which are, in turn, folded into a series of less well understood chromatin structures(1). Post-translational modifications of histone tail domains modulate chromatin structure and gene expression(2-4). Of these, histone ubiquitination is poorly understood. Here we show that the ubiquitin-conjugating enzyme Rad6 (Ubc2) mediates methylation of histone H3 at lysine 4 (Lys 4) through ubiquitination of H2B at Lys 123 in yeast (Saccharomyces cerevisiae). Moreover, H3 (Lys 4) methylation is abolished in the H2B-K123R mutant, whereas H3-K4R retains H2B (Lys 123) ubiquitination. These data indicate a unidirectional regulatory pathway in which ubiquitination of H2B (Lys 123) is a prerequisite for H3 (Lys 4) methylation. We also show that an H2B-K123R mutation perturbs silencing at the telomere, providing functional links between Rad6-mediated H2B (Lys 123) ubiquitination, Set1-mediated H3 (Lys 4) methylation, and transcriptional silencing. Thus, these data reveal a pathway leading to gene regulation through concerted histone modifications on distinct histone tails. We refer to this as 'trans-tail' regulation of histone modification, a stated prediction of the histone code hypothesis(5,6)