Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin
Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin
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DOI：
10.1016/j.molcel.2007.12.002
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发表时间：
2007-12-28
期刊：
影响因子：
16
通讯作者：
Cote, Jacques
中科院分区：
文献类型：
--
作者：
Altaf, Mohammed;Utley, Rhea T.;Cote, Jacques
Dot 1（Disruptor of telomeric silencing-1）是一种组蛋白H3赖氨酸79甲基转移酶，参与异染色质边界的建立，并与转录延伸有关。我们发现组蛋白H4 N端结构域与其他组蛋白尾部不同，与Dot 1相互作用，并且对H3 K79甲基化至关重要。此外，我们表明，异染色质蛋白Sir 3抑制Dot 1介导的甲基化，这种抑制依赖于H4的赖氨酸16。Sir 3和Dot 1结合组蛋白H4尾的相同的短的基本补丁，并且Sir 3还以甲基化敏感的方式与H3 K79周围的残基缔合。因此，Sir 3和Dot 1竞争染色质上的相同分子靶标。ChIP分析支持一种模型，其中H4赖氨酸16的乙酰化取代了Sir 3，使Dot 1结合并甲基化H3赖氨酸79，这反过来又进一步阻止了Sir 3的结合/扩散。这画出了一个详细的图片，在端粒异染色质边界的建立过程中发生的分子事件的继承。
Dot1 (Disruptor of telomeric silencing-1) is a histone H3 lysine 79 methyltransferase that contributes to the establishment of heterochromatin boundary and has been linked to transcription elongation. We found that histone H4 N-terminal domain, unlike other histone tails, interacts with Dot1 and is essential for H3 K79 methylation. Furthermore, we show that the heterochromatin protein Sir3 inhibits Dot1-mediated methylation and that this inhibition is dependent on lysine 16 of H4. Sir3 and Dot1 bind the same short basic patch of histone H4 tail, and Sir3 also associates with the residues surrounding H3 K79 in a methylation-sensitive manner. Thus, Sir3 and Dot1 compete for the same molecular target on chromatin. ChIP analyses support a model in which acetylation of H4 lysine 16 displaces Sir3, allowing Dot1 to bind and methylate H3 lysine 79, which in turn further blocks Sir3 binding/spreading. This draws a detailed picture of the succession of molecular events occurring during the establishment of telomeric heterochromatin boundaries.