WDR5 associates with histone H3 methylated at K4 and is essential for H3K4 methylation and vertebrate development
WDR5 associates with histone H3 methylated at K4 and is essential for H3K4 methylation and vertebrate development
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DOI：
10.1016/j.cell.2005.03.036
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发表时间：
2005-06-17
期刊：
影响因子：
64.5
通讯作者：
Allis, CD
中科院分区：
文献类型：
--
作者：
Wysocka, J;Swigut, T;Allis, CD
组蛋白H3赖氨酸4(K4)甲基化与多种真核生物的转录激活有关。在这里，我们证明了MLL1，ML12，和hSet1 H3 K4甲基转移酶复合体的一个共同成分，WD40-重复蛋白WDR5，直接与组蛋白H3二甲基化和三甲基化的K4和H3-K4-二甲基化的核小体结合。在人类细胞中，WDR5是甲基转移酶复合体与K4-二甲基化的H3尾巴结合所必需的，也是H3、K4三甲基化和Hox基因激活所必需的。WDR5对于脊椎动物的发育是必不可少的，因为WDR5缺失的爪哇爪哇蝌蚪表现出各种发育缺陷和空间HOX基因的异常表达。我们的结果首次证明了WD40重复蛋白作为识别特定组蛋白修饰的模块，并提出了一种读取和写入基因激活的表观遗传标记的机制。
Histone H3 lysine 4 (K4) methylation has been linked to the transcriptional activation in a variety of eukaryotic species. Here we show that a common component of MLL1, MLL2, and hSetl H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone H3 di- and trimethylated at K4 and with H3-K4-dimethylated nucleosomes. WDR5 is required for binding of the methyltransferase complex to the K4-dimethylated H3 tail as well as for global H3 K4 trimethylation and HOX gene activation in human cells. WDR5 is essential for vertebrate development, in that WDR5-depleted X. laevis tadpoles exhibit a variety of developmental defects and abnormal spatial Hox gene expression. Our results are the first demonstration that a WD40-repeat protein acts as a module for recognition of a specific histone modification and suggest a mechanism for reading and writing an epigenetic mark for gene activation.