2009年8月19日，北京生命科学研究所高绍荣实验室在Biology of Reproduction杂志在线发表题为“The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development”的文章，报道了组蛋白去甲基化酶JMJD2C在小鼠早期胚胎中的特异性表达及其在胚胎发育过程中的作用。
DNA甲基化与组蛋白修饰等表观遗传修饰在胚胎发育过程中起重要作用。尽管近几年研究发现核心组蛋白甲基化修饰具有可逆性，并发现组蛋白去甲基化酶JMJD2C可以通过调节转录因子NANOG的表达来调控小鼠ES细胞的多能性，但是关于这一新发现的组蛋白去甲基化酶在胚胎发育过程中的作用仍不清楚。该文章发现JMJD2C在小鼠早期胚胎发育过程中的表达具有时期特异性：从2-细胞期开始表达，在4-细胞期达到最高水平，并逐渐下降持续到囊胚期。该文章通过注射Jmjd2c特异的dsRNA到小鼠MII卵子中并孤雌活化，下调Jmjd2c mRNA表达水平，发现胚胎发育大部分停滞在囊胚期之前。mRNA及蛋白表达检测结果表明下调Jmjd2c mRNA表达水平可显著引起Nanog，Pou5f1和Sox2这些多能性基因，以及Myc和Klf4这些与细胞增殖相关基因的表达下调。这一结果表明胚胎早期发育停滞可能是这些基因表达变化的协同作用结果。该文章首次在证明JMJD2C不仅对ES细胞全能性具有调节作用，在小鼠胚胎早期发育中也具有重要作用。
王瑊玏(中科院动物研究所联合培养博士生)为本文的第一作者；参与此项工作的还有张苗(博士生)，张郁(技术员)，寇朝辉(技术员)和中科院动物所的韩之明和孙青原研究员。北京生命科学研究所的高绍荣博士和中科院动物研究所的陈大元研究员为本文的共同通讯作者。该研究由科技部和北京市科委资助，在北京生命科学研究所完成。（生物谷Bioon.com）
生物谷推荐原始出处：
Biology of Reproduction August 19, 2009, doi: 10.1095/?biolreprod.109.078055
The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development
Jianle Wang, Miao Zhang, Yu Zhang, Zhaohui Kou, Zhiming Han, Da-Yuan Chen, Qing-Yuan Sun and Shaorong Gao
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.
