Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms.
Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms.
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EZH1和EZH2通过不同的机制保持抑制性染色质。
DOI：
10.1016/j.molcel.2008.11.004
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发表时间：
2008-11-21
期刊：
影响因子：
16
通讯作者：
Reinberg, Danny
中科院分区：
文献类型：
--
作者：
Margueron, Raphael;Li, Guohong;Sarma, Kavitha;Blais, Alexandre;Zavadil, Jiri;Woodcock, Christopher L.;Dyniacht, Brian D.;Reinberg, Danny
多梳蛋白对维持果蝇发育过程中形成的基因抑制至关重要。该组的一部分形成含有EZ的PRC2复合体，该复合体催化组蛋白H3赖氨酸27(H3K37me2/3)的甲基化，标志着抑制转录。我们报告说，哺乳动物同源基因Ezh1和Ezh2形成了类似的PRC2复合体，但表现出相反的抑制作用。虽然PrC2-Ezh2催化H3K27me2/3，其基因敲除影响全球H3K27me2/3水平，但PrC2-Ezh1执行这一功能较弱。因此，在全球H3K27me2/3水平上，Ezh1基因敲除是无效的。相反，正如电子显微镜所证明的那样，PrC2-Ezh1直接而有力地抑制来自染色质模板的转录，并在没有甲基转移酶辅助因子SAM的情况下压缩染色质。Ezh1针对Ezh2基因的一个子集，然而Ezh1在非增殖性成年器官中更为丰富，而Ezh2的表达与增殖密切相关，这在分析老化的小鼠肾脏时得到了证明。这些结果可能反映了PcG蛋白在进化过程中的亚功能化。
Polycomb group proteins are critical to maintaining gene repression established during Drosophila development. Part of this group forms the PRC2 complex containing Ez that catalyzes methylation of histone H3 lysine 27 (H3K37me2/3), marks repressive to transcription. We report that the mammalian homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting repressive roles. While PRC2-Ezh2 catalyzes H3K27me2/3 and its knockdown affects global H3K27me2/3 levels, PRC2-Ezh1 performs this function weakly. In accordance, Ezh1 knockdown was ineffectual on global H3K27me2/3 levels. Instead, PRC2-Ezh1 directly and robustly represses transcription from chromatinized templates and compacts chromatin in the absence of the methyltransferase cofactor SAM, as evidenced by electron microscopy. Ezh1 targets a subset of Ezh2 genes, yet Ezh1 is more abundant in non-proliferative adult organs while Ezh2 expression is tightly associated with proliferation as evidenced when analyzing aging mouse kidney. These results might reflect sub-functionalization of a PcG protein during evolution.
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DOI：
10.1073/pnas.0409875102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Kuzmichev, A;Margueron, R;Reinberg, D
通讯作者：
Reinberg, D
影响因子：
16
作者：
Kuzmichev, A;Jenuwein, T;Reinberg, D
通讯作者：
Reinberg, D
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
4.8
作者：
Etchegaray, Jean-Pierre;Yang, Xiaoming;Reppert, Steven M.
通讯作者：
Reppert, Steven M.
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA