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组蛋白H4K16乙酰化调节组蛋白H3K79甲基转移酶Dot1
作者:小柯机器人 发布时间:2021/1/23 23:49:09

美国纽约大学Karim-Jean Armache研究组发现,组蛋白H4K16乙酰化调节组蛋白H3K79甲基转移酶Dot1。该项研究成果发表在2021年1月22日出版的《科学》上。

研究人员表示,Dot1(disruptor of telomeric silencing-1)是组蛋白H3第79位赖氨酸(H3K79)的甲基转移酶,其在整个进化过程中都是保守的,并在人类白血病中发生失调。

研究人员发现,组蛋白H4的乙酰化以不同于组蛋白H2B泛素化(H2BUb)但与之协调的方式变构激活酵母Dot1。研究人员进一步证明,这种激活作用是第16位赖氨酸(H4K16ac)的乙酰化,一种影响染色质结构的重要修饰。研究人员提供了这种组蛋白串扰的机制,并表明H4K16ac和H2BUb在体内和体外在H3K79二甲基和三甲基化中起关键作用。

这些数据揭示了控制H3K79甲基化的机制,并证明了H4K16ac、H3K79me和H2BUb如何共同发挥作用来调节基因转录和基因沉默,最终确保表观遗传状态的最佳维持和传播。

附:英文原文

Title: Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation

Author: Marco Igor Valencia-Sánchez, Pablo De Ioannes, Miao Wang, David M. Truong, Rachel Lee, Jean-Paul Armache, Jef D. Boeke, Karim-Jean Armache

Issue&Volume: 2021/01/22

Abstract: Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo. These data reveal mechanisms that control H3K79 methylation and demonstrate how H4K16ac, H3K79me, and H2BUb function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state.

DOI: 10.1126/science.abc6663

Source: https://science.sciencemag.org/content/371/6527/eabc6663

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037