Dot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is evolutionarily conserved in most eukaryotes. Yeast Dot1p lacks a SET domain and does not methylate free histones and thus may have different actions with respect to other histone methyltransferases. Here we show that Dot1p displays histone chaperone activity and regulates nucleosome dynamics via histone exchange in yeast. We show that a methylation-independent function of Dot1p is required for the cryptic transcription within transcribed regions seen following disruption of the Set2-Rpd3S pathway. Dot1p can assemble core histones to nucleosomes and facilitate ATP-dependent chromatin-remodeling activity through its nucleosome-binding domain, in vitro. Global analysis indicates that Dot1p appears to be particularly important for histone exchange and chromatin accessibility on the transcribed regions of long-length genes. Our findings collectively suggest that Dot1p-mediated histone chaperone activity controls nucleosome dynamics in transcribed regions.

中文翻译：

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Dot1通过其固有的组蛋白伴侣活性在酵母中调节核小体动力学。

Dot1（人类端粒沉默-1的破坏者，DOT1L）是唯一已知的负责组蛋白H3赖氨酸79甲基化（H3K79me）的酶，并且在大多数真核生物中是进化保守的。酵母Dot1p缺少SET结构域，并且不对游离的组蛋白进行甲基化，因此就其他组蛋白甲基转移酶而言可能具有不同的作用。在这里，我们显示Dot1p显示组蛋白伴侣活性，并通过酵母中的组蛋白交换调节核小体动力学。我们表明，在Set2-Rpd3S途径中断后，转录区域内的隐秘转录需要Dot1p的甲基化独立功能。Dot1p可以在体外将核心组蛋白组装成核小体，并通过其核小体结合域促进ATP依赖的染色质重塑活性。全局分析表明，Dot1p似乎对于长基因转录区域上的组蛋白交换和染色质可及性特别重要。我们的发现共同表明，Dot1p介导的组蛋白分子伴侣活性控制转录区域中的核小体动力学。