H2B泛素化在细胞重编程过程中的作用机制研究

项目名称： H2B泛素化在细胞重编程过程中的作用机制研究

项目编号： No.91519317

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 李卫

作者单位： 中国科学院动物研究所

项目金额： 75万元

中文摘要： 细胞重编程作为再生医学的研究重点目前正日益受到医学和生物学研究人员的关注。表观遗传修饰已被证明在细胞重编程过程中有重要作用。组蛋白甲基化和乙酰化作为重要的蛋白质翻译后修饰在细胞重编程的干性基因的起始以及表达等都扮演重要角色。已有研究表明，组蛋白去乙酰化酶抑制剂可以显著提高细胞重编程效率。而组蛋白泛素化在胚胎干细胞定向分化、染色质结构调节、基因转录调控、DNA损伤修复等方面都有重要作用。然而目前组蛋白泛素化在细胞重编程过程中又起到什么样的作用目前还没有报道。我们的前期研究发现，H2B泛素化在细胞重编程早期阶段发挥重要作用，本项课题将以H2B泛素化及其泛素化连接酶Rnf20作为切入点，以Rnf20条件性敲除MEF细胞来进行诱导重编程，通过ChIP-Seq和生物信息学等技术分析手段系统深入的研究组蛋白H2B泛素化在细胞编程与重编程过程中的作用机制，从而为再生医学的研究和临床应用提供理论依据。

中文关键词： H2B泛素化；诱导多能性干细胞；重编程；细胞基因网络；基因组稳定性

英文摘要： As the essential issue of ？regenerative medicine, cell reprogramming is attracting more attentions from researchers in medicine and biology. Epigenetic modification has been proven to play key roles during cell reprogramming. As one of the impotant post-translational modifications, histone methylation and acetylation are essential for pluripotent gene initiation and expression. It has been reported that inhibition of histone de-acetylation could significantly promote cell reprogramming efficiency. Ubiquitination of histones has been found essential for embroynic stem cell diffenetiation, chromatin structure regulation, gene transcription modulation and DNA damage repair. While, little is known about the role of histone ubiquitination in cell reprogramming. In our previous study, we found that histone H2B ubiquitination mainly funtions in early stage of cell reporogramming. This project will studies on the functioal role H2B ubiquitination and its E3 ligase Rnf20 during cell reprogramming by various techniques. Thus our works would not only provide a theoretical basis for regenerative medicine research,but also potential clinical applications.

英文关键词： H2B ubquitination；induced pluripotent stem cells；reprogramming；gene network；genomic stability