基于ChIA-PET系统解析猪骨骼肌卫星细胞3D基因组成肌分化调控机制

项目名称： 基于ChIA-PET系统解析猪骨骼肌卫星细胞3D基因组成肌分化调控机制

项目编号： No.31472074

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 畜牧学与草地科学

项目作者： 曹建华

作者单位： 华中农业大学

项目金额： 86万元

中文摘要： 研究基因的调控模式是研究其机制的重要内容。通过ChIA-PET系统研究3D基因组调控区的远程相互作用模式，在人和小鼠基因组调控的研究中已大获成功，但在猪上的研究却还未起步。本项目在猪骨骼肌原代卫星细胞分离和培养的基础上，通过ChIA-PET系统对转录元件RNAPII和转录因子MyoD的位点进行3D基因组调控模式分析，在全基因组层面上从基因转录调控的水平挖掘肌卫星细胞成肌分化过程的调控机制，构建3D基因组调控网络模型，建立基因调控模式与成肌分化机制间的内在联系，从基因组调控的角度研究猪骨骼肌卫星细胞成肌分化的重要特征，并通过功能实验验证远程调控位点。以期初步阐明肌卫星细胞成肌分化的基本规律，探索猪肌肉生长发育的时空特性，解析3D基因组远程调控模式的生物学效应。为进一步研究肌卫星细胞成肌分化与肌肉生长发育间的精细调控机制奠定基础，从而为深入研究猪骨骼肌生长发育的调控机制和发育模式提供理论支持。

中文关键词： 猪；3D基因组；ChIA-PET；卫星细胞；调控机制

英文摘要： The research on gene regulations is the precondition of dissecting gene functions. There is a tremendous success in the studies of human and mice which research on the remote regulatory interactions at the level of 3D genome by using ChIA-PET system. However, it has not yet started in pig genome. On the basis of isolation and culture of primary satellite cells of porcine skeletal muscle, this work will investigate the 3D genomics myogenesis mechanisms via ChIA-PET system for transcriptional element RNAPII and transcript factor MyoD, analyze the myogenesis regulation from the point of whole genome transcription levels, and construct the networks model of 3D genome, establish the intrinsically relationship between regulation pattern and the myogenesis mechanisms, determine vital myogenesis characters of the porcine muscular satellite cells in terms of genomic regulation, and validate remote interaction sites by functional assays. This work will elucidate the myogenesis fundamental laws of the satellite cells which are associated with muscle space-time development, and interpret the biological meaning of the remote regulatory models. Moreover, this work will contribute further research on refining regulatory mechanisms between myogenesis of the satellite cells and muscle development, and provide a theoretical basis for discovering novel regulatory mechanism and patterns of porcine skeletal muscle development.

英文关键词： pig;3D genome;ChIA-PET;satellite cells;regulatory mechanism