Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression
Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression
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DOI：
10.1016/j.molcel.2005.07.024
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发表时间：
2005-09-16
期刊：
影响因子：
16
通讯作者：
Shilatifard, A
中科院分区：
文献类型：
--
作者：
Schneider, J;Wood, A;Shilatifard, A
含有set1的复合物COMPASS是人类MLL复合物的酵母同源物，是组蛋白H3赖氨酸4的单、二和三甲基化所必需的。我们进行了比较的全球蛋白质组学筛选，以更好地定义COMPASS在组蛋白三甲基化中的作用。我们报道COMPASS的Cps60和Cps40组分都是组蛋白H3三甲基化所必需的，而不是端粒相关基因沉默的适当调节。缺乏Cps60的纯化COMPASS可以单甲基化和二甲基化，但不能三甲基化H3（K4）。染色质免疫沉淀（ChIP）研究表明，组蛋白三甲基化所需的COMPASS亚基缺失并不影响所测试基因Set1在染色质上的定位。总的来说，我们的研究结果表明，COMPASS的几个组成部分对组蛋白H3三甲基化和端粒相关基因表达的调节是分子必需的，这表明COMPASS在不同形式的组蛋白甲基化中具有多种作用。
The Set1-containing complex COMPASS, which is the yeast homolog of the human MLL complex, is required for mono-, di-, and trimethylation of lysine 4 of histone H3. We have performed a comparative global proteomic screen to better define the role of COMPASS in histone trimethylation. We report that both Cps60 and Cps40 components of COMPASS are required for proper histone H3 trimethylation, but not for proper regulation of telomere-associated gene silencing. Purified COMPASS lacking Cps60 can monoand dimethylate but is not capable of trimethylating H3(K4). Chromatin immunoprecipitation (ChIP) studies indicate that the loss subunits of COMPASS required for histone trimethylation do not affect the localization of Set1 to chromatin for the genes tested. Collectively, our results suggest a molecular requirement for several components of COMPASS for proper histone H3 trimethylation and regulation of telomere-associated gene expression, indicating multiple roles for different forms of histone methylation by COMPASS.