Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS
Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS
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DOI：
10.1016/j.cell.2007.09.046
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发表时间：
2007-12-14
期刊：
影响因子：
64.5
通讯作者：
Shilatifard, Ali
中科院分区：
文献类型：
--
作者：
Lee, Jung-Shin;Shukla, Abhijit;Shilatifard, Ali
COMPASS是哺乳动物MLL复合体的酵母同源物，是一种组蛋白H3赖氨酸4(H3K4)甲基酶，由Set1(KMT2)和其他7种多肽组成，其中Cps35是唯一的必需亚基。COMPASS的H3K4甲基化和Dot1的H3K79甲基化都需要RAD6/Bre1对组蛋白H2 B进行单素化。然而，这种组蛋白串扰的分子机制却知之甚少。在这里，我们证明了组蛋白H2B的单泛素化控制了Cps35与COMPASS复合体的结合。COMPASS在体内的催化活性需要CPS 35，而将外源纯化的Cps 35加入到从Delta rad6背景中纯化的COMPASS中会产生甲基化能力的COMPASS。Cps35与COMPASS调控基因的染色质以H2BK123单泛素依赖但不依赖于Set1的方式相关联。正确的H3K79三甲基化也需要Cps35。这些发现提供了对Cps35在将H2 B单泛素化信号转换为H3甲基化信号中的分子作用的洞察。
COMPASS, the yeast homolog of the mammalian MLL complex, is a histone H3 lysine 4 (H3K4) methylase consisting of Set1 (KMT2) and seven other polypeptides, including Cps35, the only essential subunit. Histone H2B monoubiquitination by Rad6/Bre1 is required for both H3K4 methylation by COMPASS, and H3K79 methylation by Dot1. However, the molecular mechanism for such histone crosstalk is poorly understood. Here, we demonstrate that histone H2B monoubiquitination controls the binding of Cps35 with COMPASS complex. Cps 35 is required for COMPASS' catalytic activity in vivo, and the addition of exogenous purified Cps35 to COMPASS purified from a Delta rad6 background results in the generation of a methylation competent COMPASS. Cps35 associates with the chromatin of COMPASS-regulated genes in a H2BK123 monoubiquitination-dependent but Set1-independent manner. Cps35 is also required for proper H3K79 trimethylation. These findings offer insight into the molecular role of Cps35 in translating the H2B monoubiquitination signal into H3 methylation.