Chromatin signaling to kinetochores: transregulation of Dam1 methylation by histone H2B ubiquitination.

Chromatin signaling to kinetochores: transregulation of Dam1 methylation by histone H2B ubiquitination.
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DOI:
10.1016/j.cell.2011.07.025
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发表时间:
2011-09-02
期刊:
影响因子:
64.5
通讯作者:
Dent SY
Dent SY
中科院分区:
生物学1区
文献类型:
--
作者:
Latham JA;Chosed RJ;Wang S;Dent SY

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组蛋白H3K4由Set1/MLL家族蛋白三甲基化提供了从酵母到人类转录活性的标志。在酿酒酵母中,H3K4甲基化是由含有Set1的COMPASS复合体介导的,并受组蛋白H2BK123先前泛素化的反式调节。所有调节H2BK123ub和H3K4me的事件都被认为发生在基因启动子上。在这里,我们报告,这一途径对于Set1唯一已知的另一底物K233的甲基化是必不可少的,在DAM1中,在运动中心。RAD6、Bre1或Paf1复合体成员的缺失会取消Dam1的甲基化,就像H2 BK123的突变一样。我们的结果表明,Set1介导的甲基化受一条与底物无关的一般途径的调控,该途径由独立于转录发挥作用的转录调节因子组成。此外,我们的数据确定了组蛋白修饰和非组蛋白修饰之间的反式调节串扰节点,表明染色质状态的变化可以发出其他基本细胞蛋白和机制功能变化的信号。
Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory cross-talk in trans between a histone modification and modification on a non-histone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries.
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