Different Ezh2-containing complexes target methylation of histone H1 or nucleosomal histone H3
Different Ezh2-containing complexes target methylation of histone H1 or nucleosomal histone H3
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DOI：
10.1016/s1097-2765(04)00185-6
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发表时间：
2004-04-23
期刊：
影响因子：
16
通讯作者：
Reinberg, D
中科院分区：
文献类型：
--
作者：
Kuzmichev, A;Jenuwein, T;Reinberg, D
人Zeste同源增强子（Ezh2）是一种与转录抑制相关的组蛋白赖氨酸甲基转移酶（HKMT）。Ezh2存在于几种不同的复合物中，其中之一PRC2，我们之前描述过。这里我们报告了另一个Ezh2复合物PRC3。我们发现Ezh2复合物对赖氨酸甲基化的特异性历史表现出不同的靶向性，这取决于组蛋白底物的背景。这种不同的靶向是每个复合物中相关Eed蛋白的功能。我们发现Eed蛋白存在于四种亚型中，这代表了同一mRNA的不同翻译起始位点的使用。这些Eed亚型选择性地与不同的含ezh2复合物结合，从而导致其相关的HKMT活性对组蛋白H3-K27或组蛋白H1-K26的差异靶向。我们的数据为通过调节亚基的不同翻译产物调节染色质修饰酶的底物特异性的新机制提供了证据。
Human Enhancer of Zeste homolog (Ezh2) is a histone lysine methyltransferase (HKMT) associated with transcriptional repression. Ezh2 is present in several distinct complexes, one of which, PRC2, we characterized previously. Here we report an additional Ezh2 complex, PRC3. We show that the Ezh2 complexes exhibit differential targeting of specific histories for lysine methylation dependent upon the context of the histone substrates. This differential targeting is a function of the associated Eed protein within each complex. We found that Eed protein is present in four isoforms, which represent alternate translation start site usage from the same mRNA. These Eed isoforms selectively associate with distinct Ezh2-containing complexes with resultant differential targeting of their associated HKMT activity toward histone H3-K27 or histone H1-K26. Our data provide evidence for a novel mechanism regulating the substrate specificity of a chromatin-modifying enzyme through disparate translational products of a regulatory subunit.