The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules
The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules
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DOI：
10.1038/nsmb.1384
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发表时间：
2008-03-01
影响因子：
16.8
通讯作者：
Cheng, Xiaodong
中科院分区：
文献类型：
--
作者：
Collins, Robert E.;Northrop, Jeffrey P.;Cheng, Xiaodong
组蛋白修饰在转录控制、有丝分裂和异染色质形成中起重要作用。G9a和G9a样蛋白（GLP）是常染色质相关的甲基转移酶，通过在Lys9 （H3K9）上单甲基化和二甲基化组蛋白H3来抑制转录。在这里，我们证明了G9a和GLP的锚蛋白重复结构域与含有单甲基或二甲基K9的n端H3肽的强烈偏好结合。x射线晶体学揭示了由三个色氨酸和一个酸性残基组成的部分疏水笼识别甲基化赖氨酸的基础。笼中关键残基的替换消除了H3尾部相互作用。因此，G9a和GLP含有一种新型的甲基赖氨酸结合模块（锚蛋白重复结构域），并且是在单个多肽中具有产生和读取相同表观遗传标记活性的蛋白质（组蛋白）甲基转移酶的第一个例子。
Histone modifications have important roles in transcriptional control, mitosis and heterochromatin formation. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by mono- and dimethylating histone H3 at Lys9 (H3K9). Here we demonstrate that the ankyrin repeat domains of G9a and GLP bind with strong preference to N-terminal H3 peptides containing mono- or dimethyl K9. X-ray crystallography revealed the basis for recognition of the methylated lysine by a partial hydrophobic cage with three tryptophans and one acidic residue. Substitution of key residues in the cage eliminated the H3 tail interaction. Hence, G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.