组蛋白H2A泛素E3连接酶Bmi1和Mel18在胚胎着床中的作用

项目名称： 组蛋白H2A泛素E3连接酶Bmi1和Mel18在胚胎着床中的作用

项目编号： No.31200881

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生理学与整合生物学

项目作者： 王维香

作者单位： 中国科学院动物研究所

项目金额： 23万元

中文摘要： 胚泡植入过程由复杂的调控网络控制，涉及到多个功能基因的开启和关闭。在参与这些功能基因的转录调控中，染色质重塑尤其是组蛋白修饰占据着核心位置。Polycomb是一类保守的组蛋白修饰抑制因子，其产物调控Hox基因的表达。Polycomb基因家族主要包括PRC1和PRC2两类复合体。已知PRC1复合体核心组分Bmi1和Mel18具有组蛋白H2A 泛素连接酶活性，并对干细胞和生殖细胞的自我更新具有重要意义。我们先期研究发现Bmi1和Mel18敲除小鼠对胚泡植入等生殖过程有重要影响，但其具体的生理机制还不得而知。本项目拟利用转基因和条件性敲除小鼠模型开展如下研究：① Bmi1和Mel18在植入前胚胎和围植入期子宫中的动态表达模式；② Bmi1和Mel18对胚泡植入等关键功能基因的表观遗传调控机制；③ Bmi1和Mel18对子宫内膜蜕膜化的调节机制，以期揭示和丰富小鼠胚泡植入等生殖过程的分子调控机理。

中文关键词： 植入；泛素化；Bmi-1和 Mel18；组蛋白H2A；蜕膜

英文摘要： In placental mammals, blastocyte implantation into uterine lining occurs through highly complex and orchestrated processes that gene expression and repression of multiple regulated genes are involved. In the recent years, researches indicate that chromatin modifications, such as histone modifications and DNA methylation, play key important roles in the epigenetic regulation of gene expression and repression. Polycomb group proteins were identified as a conserved chromation modification repressor whose products are required in multimeric complexes to matintain spatially restricted expression of Hox cluster genes. Polycomb group proteins exist in at least two biochemically distinct protein complexes, the histone H2A ubiquitinationase PRC1 complex and the EED-EZH2 complex. Bmi1 and Mel18 are critical components of PRC1, and play important roles in regulating self-renewal of stem cell and germ cell. Our previous data show that mice deficient for Mel18 or Bmi1 exhibit severe deficiency for blastocye implantation. However,the physiological mechanisms of Bmi1 and Mel18 in blastocyte implantation and uterus decidualization are unknown. We will use tansgenic and uterine conditional kncock out mice model to identity and characterize function of Bmi1 and Mel18 at such aspects: ① Dynamic expression pattern in the period o

英文关键词： implantation；Ubiqitination；Bmi-1和 Mel18；Histone H2A；decidualization