肝癌细胞上皮间质转化过程中Snai1介导的染色质长程作用与转录抑制

项目名称： 肝癌细胞上皮间质转化过程中Snai1介导的染色质长程作用与转录抑制

项目编号： No.31301044

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 陈阳

作者单位： 清华大学

项目金额： 25万元

中文摘要： Snai1是上皮间质转化过程中的一个关键转录抑制因子，能够形成转录抑制复合体介导启动子区的染色质重塑，控制下游众多靶基因。然而目前尚为见报道直接证实，Snai1在抑制不同靶基因转录的过程中是否存在关联。因此，我们将结合ChIA-PET，ChIP-Seq等组学技术，在肝癌细胞上皮间质转化过程中，时序地分析Snai1调控下的染色质相互作用组；将Snai1介导的染色质长程作用与转录抑制过程中的转录信号（H3K4me3和Pol II）和染色质重塑信号（H3K4me2、H3-Ac、H3K27me3、H3K9me2）进行时序关联分析，筛选出可能调控转录抑制的染色质长程作用；通过构建染色质长程相互作用网络，描述染色质长程作用间关系； 并进一步通过分子生物学实验分析Snai1介导的染色质长程作用与基因转录抑制的关系，期望回答在肝癌细胞上皮间质转化过程中Snai1对不同靶基因的抑制是否存在着关联。

中文关键词： 上皮间质转化；三维基因组；染色质相互作用；纳米材料；

英文摘要： As a key transcriptional repressor during epithelial-mesenchymal transition(EMT), Snai1 has been shown to recruit the transcriptional repressor complex to induce the chromatin remodeling at the promoter of its targets and then the expression is closed. It has been report that there are many genes are Snai1's target during EMT, however, there is no result to show if there is relationship between the processes of Snai1 closing different targets. During the EMT of liver cancer cells, ChIA-PET and ChIP-Seq will be used to capture a time series chromatin interactomes of Snai1. And then, to find out the functional long-range chromatin interaction induced by Snai1, we will analysis the relationship between all interactions induced by Snai1 and gene transcriptional signaling (H3K4me3 and Pol II) and chromatin remodeling signaling (H3K4me2, H3-Ac, H3K27me3, H3K9me2also) by time series correlation analysis algorithm. Then, the candidates will be used to long-range chromatin interaction network construction. After network analysis, we will focus on those key interactions and try to illustrate the relationship between these Snai1 induced chromatin interaction and Snai1 induced repression by bench work. At last, we will answer the question if there is relationship between the processes of Snai1 closing different targets.

英文关键词： EMT；3D Genome；chromatin interaction；Nano materals；