Montgomery Nathan D, Yee Della, Chen Andrew, Kalantry Sundeep, Chamberlain Stormy J, Otte Arie P, Magnuson Terry
Department of Genetics, University of North Carolina at Chapel Hill, Call Box #7264, Chapel Hill, North Carolina 27599, USA.
Curr Biol. 2005 May 24;15(10):942-7. doi: 10.1016/j.cub.2005.04.051.
PcG proteins mediate heritable transcriptional silencing by generating and recognizing covalent histone modifications. One conserved PcG complex, PRC2, is composed of several proteins including the histone methyltransferase (HMTase) Ezh2, the WD-repeat protein Eed, and the Zn-finger protein Suz12. Ezh2 methylates histone H3 on lysine 27 (H3K27), which serves as an epigenetic mark mediating silencing. H3K27 can be mono-, di-, or trimethylated (1mH3K27, 2mH3K27, and 3mH3K27, respectively). Hence, either PRC2 must be regulated so as to add one methyl group to certain nucleosomes but two or three to others, or distinct complexes must be responsible for 1m-, 2m-, and 3mH3K27. Consistent with the latter possibility, 2mH3K27 and 3mH3K27, but not 1mH3K27, are absent in Suz12-/- embryos, which lack both Suz12 and Ezh2 protein. Mammalian proteins required for 1mH3K27 have not been identified. Here, we demonstrate that unlike Suz12 and Ezh2, Eed is required not only for 2m- and 3mH3K27 but also global 1mH3K27. These results provide a functionally important distinction between PRC2 complex components and implicate Eed in PRC2-independent histone methylation.
多梳蛋白（PcG）通过产生和识别共价组蛋白修饰来介导可遗传的转录沉默。一种保守的PcG复合物PRC2由几种蛋白质组成，包括组蛋白甲基转移酶（HMTase）Ezh2、WD重复蛋白Eed和锌指蛋白Suz12。Ezh2使组蛋白H3的赖氨酸27（H3K27）甲基化，这作为一种介导沉默的表观遗传标记。H3K27可以被单甲基化、二甲基化或三甲基化（分别为1mH3K27、2mH3K27和3mH3K27）。因此，要么必须对PRC2进行调控，以便在某些核小体上添加一个甲基，但在其他核小体上添加两个或三个甲基，要么不同的复合物必须负责1mH3K27、2mH3K27和3mH3K27的形成。与后一种可能性一致，在缺乏Suz12和Ezh2蛋白的Suz12-/-胚胎中不存在2mH3K27和3mH3K27，但存在1mH3K27。尚未鉴定出形成1mH3K27所需的哺乳动物蛋白。在这里，我们证明，与Suz12和Ezh2不同，Eed不仅是形成2mH3K27和3mH3K27所必需的，也是形成整体1mH3K27所必需的。这些结果在PRC2复合物组分之间提供了一个功能上重要的区别，并表明Eed参与了不依赖PRC2的组蛋白甲基化过程。
