Lee Soyun, Oh Seunghee, Jeong Kwiwan, Jo Hyelim, Choi Yoonjung, Seo Hogyu David, Kim Minhoo, Choe Joonho, Kwon Chang Seob, Lee Daeyoup
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Biocenter, Gyeonggi Business & Science Accelerator, Suwon, Gyeonggi-do, 16229, Republic of Korea.
Nat Commun. 2018 Jan 16;9(1):240. doi: 10.1038/s41467-017-02759-8.
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.
Dot1（端粒沉默破坏因子-1，人类中为DOT1L）是已知唯一负责组蛋白H3赖氨酸79甲基化（H3K79me）的酶，在大多数真核生物中具有进化保守性。酵母Dot1p缺乏SET结构域，不会使游离组蛋白甲基化，因此相对于其他组蛋白甲基转移酶可能具有不同的作用。在此我们表明，Dot1p在酵母中表现出组蛋白伴侣活性，并通过组蛋白交换调节核小体动力学。我们表明，在Set2-Rpd3S途径破坏后在转录区域中观察到的隐蔽转录需要Dot1p的非甲基化依赖性功能。在体外，Dot1p可以将核心组蛋白组装成核小体，并通过其核小体结合结构域促进ATP依赖的染色质重塑活性。全局分析表明，Dot1p对于长基因转录区域上的组蛋白交换和染色质可及性似乎特别重要。我们的研究结果共同表明，Dot1p介导的组蛋白伴侣活性控制转录区域中的核小体动力学。
