The Polycomb-group gene Ezh2 is required for early mouse development
The Polycomb-group gene Ezh2 is required for early mouse development
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DOI：
10.1128/mcb.21.13.4330-4336.2001
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发表时间：
2001-07-01
影响因子：
5.3
通讯作者：
Jenuwein, T
中科院分区：
文献类型：
--
作者：
O'Carroll, D;Erhardt, S;Jenuwein, T
多梳组（Pc-G）基因是稳定抑制同源异型选择基因和其他发育调控基因所必需的，可能是通过调节染色质结构域。在果蝇Pc-G基因中，Zeste [E（z）]增强子值得特别考虑，因为它代表了进化中最保守的Pc-G基因之一。此外，E（Z）蛋白家族包含SET结构域，其最近与组蛋白甲基转移酶（HMTase）活性相关。虽然E（Z）相关蛋白尚未与HMTase活性直接相关，但哺乳动物Ezh 2是组蛋白脱乙酰酶复合物的成员。为了研究其体内功能，我们产生了Ezh 2缺陷小鼠。Ezh 2无效突变在小鼠发育的早期阶段导致致死性。Ezh 2突变小鼠要么在植入后停止发育，要么启动但未能完成原肠胚形成。此外，Ezh 2缺陷的胚泡显示出受损的生长潜力，阻止Ezh 2缺失的胚胎干细胞的建立。有趣的是，Ezh 2在受精后上调，并在小鼠发育的着床前阶段保持高度表达。总之，这些数据表明Ezh 2在小鼠早期发育中的重要作用，并将Ezh 2与eed和YY 1（唯一的其他早期作用的Pc-G基因）遗传联系起来。
Polycomb-group (Pc-G) genes are required for the stable repression of the homeotic selector genes and other developmentally regulated genes, presumably through the modulation of chromatin domains. Among the Drosophila Pc-G genes, Enhancer of zeste [E(z)] merits special consideration since it represents one of the Pc-G genes most conserved through evolution. In addition, the E(Z) protein family contains the SET domain, which has recently been linked with histone methyltransferase (HMTase) activity. Although E(Z)-related proteins have not (yet) been directly associated with HMTase activity, mammalian Ezh2 is a member of a histone deacetylase complex. To investigate its in vivo function, we generated mice deficient for Ezh2. The Ezh2 null mutation results in lethality at early stages of mouse development. Ezh2 mutant mice either cease developing after implantation or initiate but fail to complete gastrulation. Moreover, Ezh2-deficient blastocysts display an impaired potential for outgrowth, preventing the establishment of Ezh2-null embryonic stem cells. Interestingly, Ezh2 is up-regulated upon fertilization and remains highly expressed at the preimplantation stages of mouse development. Together, these data suggest an essential role for Ezh2 during early mouse development and genetically link Ezh2 with eed and YY1, the only other early-acting Pc-G genes.