The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development
The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development
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组蛋白去甲基化酶 JMJD2C 在植入前小鼠胚胎中阶段特异性表达，并且是胚胎发育所必需的
DOI：
10.1095/biolreprod.109.078055
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发表时间：
2010-01-01
影响因子：
3.6
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Wang, Jianle;Zhang, Miao;Gao, Shaorong
表观遗传修饰通过动态调节DNA甲基化和染色质修饰在胚胎发育中起关键作用。虽然最近的研究表明核心组蛋白甲基化是可逆的，但很少有研究调查新发现的组蛋白去甲基化酶在胚胎发育过程中的功能。在本研究中，我们研究了组蛋白去甲基化酶JMJD2C，属于JmjC结构域的组蛋白去甲基化酶，在小鼠植入前胚胎发育过程中的表达特征和功能。我们发现，JMJD2C是阶段特异性表达在植入前的发展，与最高的活动被观察到从两个细胞到八个细胞的阶段。在中期II卵母细胞中耗尽JMJD2C，然后孤雌激活，导致胚泡阶段之前的发育停滞。此外，与先前在胚胎干（ES）细胞中的发现一致，JMJD2C的耗尽导致胚胎中多能性基因Nanog的显著下调。然而，与先前在ES细胞中的报道相反，我们观察到其他多能性基因Pou5f1和Sox 2在JM JD2C耗尽的胚胎中也显著下调。此外，早期胚胎中JMJD2C的消耗还引起与细胞增殖相关的Myc和Klf4基因的显著下调。我们的数据表明，这些关键基因的失调协同导致在JMJD2C耗尽胚胎中观察到的发育缺陷。
Epigenetic modifications play a pivotal role in embryonic development by dynamically regulating DNA methylation and chromatin modifications. Although recent studies have shown that core histone methylation is reversible, very few studies have investigated the functions of the newly discovered histone demethylases during embryonic development. In the present study, we investigated the expression characteristics and function of JMJD2C, a histone demethylase that belongs to the JmjC-domain-containing histone demethylases, during preimplantation embryonic development of the mouse. We found that JMJD2C is stage-specifically expressed during preimplantation development, with the highest activity being observed from the two-cell to the eight-cell stage. Depletion of JMJD2C in metaphase II oocytes followed by parthenogenetic activation causes a developmental arrest before the blastocyst stage. Moreover, consistent with a previous finding in embryonic stem (ES) cells, depletion of JMJD2C causes a significant down-regulation of the pluripotency gene Nanog in embryos. However, contrary to a previous report in ES cells, we observed that other pluripotency genes, Pou5f1 and Sox2, are also significantly down-regulated in JMJD2C-depleted embryos. Furthermore, the depletion of JMJD2C in early embryos also caused significant down- regulation of the Myc and Klf4 genes, which are associated with cell proliferation. Our data suggest that the deregulation of these critical genes synergistically causes the developmental defects observed in JMJD2C-depleted embryos.