NURF重塑复合物调控iPS细胞重编程作用及表观遗传机制研究

项目名称： NURF重塑复合物调控iPS细胞重编程作用及表观遗传机制研究

项目编号： No.91419308

项目类型： 重大研究计划

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 范祖森

作者单位： 中国科学院生物物理研究所

项目金额： 200万元

中文摘要： 细胞重编程的表观遗传机制研究是干细胞领域研究的热点。我们前期研究发现，自噬过程对于iPS细胞重编程至关重要。自噬发生在iPS诱导的第1-2天，并发现Sox2通过招募NuRD复合物结合到mTOR基因的启动子区下调mTOR的表达。自iPS诱导的第3天后，自噬和mTOR恢复至稳态水平。我们进一步研究发现，在iPS诱导后期mTOR启动子区结合NURF复合物。沉默NURF复合物组分的表达均下调mTOR的表达，并且阻止了iPS细胞的形成，表明NURF复合物在细胞重编程中发挥着重要的调节作用。在此基础上，本项目将探明NURF复合物对iPS细胞重编程的调控作用，揭示NURF复合物对mTOR基因表达的调节作用及与细胞重编程诱导的关系，阐明NURF复合物调控细胞重编程的表观遗传机制。以期揭示iPS细胞诱导形成的分子机制，为提高iPS细胞的诱导效率和质量提供理论基础。

中文关键词： 细胞重编程；癌变重编程；NURF复合物；表观遗传调控；分子机制

英文摘要： The epigenetic mechanisms of cell reprogramming have recently become a hot research field in the stem cell study. In an our previous study, we found that autophagy is essential for the reprogramming of iPSC. During the first 1-2 days of iPSC induction, Sox2 recruits the NuRD complex to the promoter of mTOR to repress its expression. After three days’ induction, the levels of mTOR and autophagy return to a basal level. We further found that the NURF complex binds to the promoter of mTOR. Silencing of the components of NURF complex reduces the expression level of mTOR and inhibits the formation of iPSC, indicating that the NURF complex is required for cell reprogramming. Based on our previous studies, we will reveal the regulation role of NURF complex in the induction of cell reprogramming, veryfy the relationship between the NURF complex and mTOR expression, and explore the epigenetic mechanisms involved in the cell reprogramming. By this project, we will reveal a noval molecular mechanism underlying iPS reprogramming, and provide theoretical basis to improve the efficiency and quality of iPSC generation. This project conforms to the reserch requirement of “The epigenetic mechanisms of cell reprogramming” proposed by 2014 Major Program of National Natural Science Foundation of China.

英文关键词： cell reprogramming；oncogenetic reprogramming；NURF remodeling complex；epigenetic regulation；molecular mechanism