WD重复结构域5（WDR5）与在赖氨酸4（K4）处发生甲基化的组蛋白H3相关联，并且对于H3 K4甲基化和脊椎动物发育至关重要。

WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development.

作者信息

Wysocka Joanna, Swigut Tomek, Milne Thomas A, Dou Yali, Zhang Xin, Burlingame Alma L, Roeder Robert G, Brivanlou Ali H, Allis C David

机构信息

Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA.

出版信息

Cell. 2005 Jun 17;121(6):859-72. doi: 10.1016/j.cell.2005.03.036.

DOI:10.1016/j.cell.2005.03.036

PMID:15960974

Abstract

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 hSet1 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.

摘要

组蛋白H3赖氨酸4（K4）甲基化与多种真核生物物种的转录激活相关。在此我们表明，MLL1、MLL2和hSet1 H3 K4甲基转移酶复合物的一个共同组分，WD40重复蛋白WDR5，直接与在K4处二甲基化和三甲基化的组蛋白H3以及与H3-K4-二甲基化核小体结合。WDR5是甲基转移酶复合物与K4-二甲基化H3尾部结合所必需的，也是人类细胞中整体H3 K4三甲基化和HOX基因激活所必需的。WDR5对脊椎动物发育至关重要，因为WDR5缺失的非洲爪蟾蝌蚪表现出多种发育缺陷和异常的空间Hox基因表达。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用于基因激活的表观遗传标记的机制。