细胞分化过程中长非编码RNA介导的三维基因组遗传信息传递网络的解析

The genome of higher eukaryotes can only effectively and accurately complete its basic biological function after be finely folded into a specific three-dimensional configuration in nuclears. The long-noncoding RNAs that are transcripted from distal non-coding regulatory regions have been shown to be involving in the establishment, maintenance of the three-dimensional genome configuration, as well as involving in the exchanging of genetic information within the nuclear. Together with other regulatory elements, the long-noncoding RNAs and the genomic interactions constitute the three-dimensional genetic information transmission network. However, there is still a lack of research on this network, and the basic operating mechanism is poorly understood. In recent years, with the promotion of new technology, the research on the long-noncoding RNA mediated three-dimensional genome information transmission network has become a new research front. To construct the long-noncoding RNA mediated three-dimensional genome information transmission network, this project intended to improve the Hi-C experimental technology and, combined with the transcriptome and epigenome data, to develop a new computational method for data integration. Based on these novel technologies, the project will develop a new algorithm to identify the key long-noncoding RNAs in a given biological process. Finally, by applying the newly developed computational and experimental techniques onto the 3T3-L1 model, which is a mouse adipose precursor cell line, the project will identify the key long-noncoding RNA in the process of adipose development. In this project, a new method which is based on the perspective of three-dimensional genome genetic information transmission network is proposed to study the long-noncoding RNAs. This perspective provides a novel strategy to functional survey of the long-noncoding RNAs.

高等生物的基因组只有被精细的折叠成特定三维空间构型才能有效而精确的完成基本的生物学功能。而远端非编码区转录的长非编码RNA参与了此三维基因组空间构型的建立、维持、和遗传信息的交互， 并和其他调控元件一起构成了三维基因组遗传信息传递网络。然而，目前对这一网络还缺少研究，对其基本运行机制更是知之甚少。近年来在新技术的推动下，解析长非编码RNA介导的三维基因组遗传信息传递网络成为新的研究热点。本项目拟改进Hi-C实验技术和开发新的计算方法，结合多组学数据，构建细胞分化过程中长非编码RNA介导的三维基因组信息传递网络。通过解析该网络，本项目将开发识别细胞分化过程中关键长非编码RNA的新算法。最后，以小鼠脂肪前体细胞3T3-L1分化过程为模型，鉴定在此过程中关键长非编码RNA。本项目从三维基因组遗传信息传递网络为视角考察长非编码RNA，为长非编码RNA的功能研究提供了全新的思路。

高等生物的基因组的高级空间结构蕴含丰富的调控信息，而RNA在这一信息传递过程中扮演着重要的角色，尤其是非编码区转录的长非编码RNA参与了此三维基因组空间构型的建立、维持、和遗传信息的交互，并和其他调控元件一起构成了三维基因组遗传信息传递网络。然而，目前对这一网络还缺少研究，对其基本运行机制更是知之甚少。近年来在新技术的推动下，解析长非编码RNA介导的三维基因组遗传信息传递网络成为新的研究热点。本项目结合多组学数据，开发了新的计算方法来解析这一网络。我们通过整合核小体排布的信息开发了预测远距离染色质相互作用的算法（CISD），我们通过整合网络结构信息熵方法开发了推断染色质高级结构的算法（deDoc）。此基础上，我们开发了三维基因组的可靠黄金数据集数据库3CDB, 和基于云平台的三维基因组可视化方法(Delta)。利用上述工具，我们研究了远程基因组位点上转录的非编码RNA，我们发现反式剪接和基因组三维空间结构高度相关，反式剪接可以作为一种重要的调控信息传递机制。本项目从三维基因组遗传信息传递网络为视角考察长非编码RNA，为长非编码RNA的功能研究提供了全新的思路。