超级增强子是新发现的一类新型基因调控元件，它能够通过调控关键基因，决定细胞的属性和命运，调节生长分化。研究表明超级增强子与人类多种重要疾病密切相关，并通过特有的方式参与多种癌症的调控，具有重要的学术研究价值和医学应用前景，但目前对超级增强子的研究主要停留在细胞水平。本研究结合前期研究基础，拟利用转座子介导技术，构建斑马鱼精子插入突变体库，进行斑马鱼超级增强子分离鉴定，获取斑马鱼超级增强子基础数据，并利用CRISPR/Cas9基因组修饰技术进行典型超级增强子核心元件敲除，在胚胎和活体水平开展超级增强子功能研究。项目拟率先尝试在斑马鱼胚胎和个体水平进行超级增强子挖掘和功能解析研究，为将来整体解析斑马鱼细胞和组织超级增强子蓝图目录，深入揭示其对生长发育调控的分子机制奠定基础，并为其在人类医学中的应用研究提供参考。拟申请专利1-2项，发表SCI论文2-4篇，培养研究生3-5人，研究骨干2-3人。

Super enhancer is a new type of gene regulatory element discovered recently, it can decide the attribute and fate of cells, and regulates cell growth and differentiation through the regulation of key genes. Studies have shown that super enhancer is closely related to a variety of human diseases, and participate in the regulation of a variety of cancers through a unique way. Therefore, super enhancer research has important academic value and application prospect in medicine, but the current study on super enhancer mainly stays at the cellular level. Based on the previous research, this project intends to use transposon mediated technique to construct sperm insertion mutagenesis library in zebrafish; then to isolate and identify the super enhancers in zebrafish cells and tissues. Then the CRISPR / cas9 genome modification technology will be used to knockout the core component of typical super enhancer to investigate the function of super enhancer in embryo and in vivo levels. This project aims to mine super enhancer in zebrafish and conduct the functional analysis of super enhancer in embryo and individual level at first time, which will set up the research basic for the future global annotation of the super enhancer directory in zebrafish cells and tissues, and understanding of the molecular mechanisms of super enhancer in regulation of cell and embryo development. And these results will provide the reference for the application research of super enhancer in human medicine. This study is planning to apply for 1-2 patents, publish 2-4 high IF SCI papers, and train 2-3 core researchers, and 3-5 graduate students.