表观修饰、染色质三维结构与核空间定位均对基因表达具有调控作用，且三者间相互可调控，但是，它们在细胞命运决定中如何协同发挥功能及其调控机制仍不清楚。因此，为充分解析相同表观修饰的染色质由于三维互作，形成具有核空间分布结构域的现象，我们提出核空间表观结构域（N-SIDE）的概念。近期我们通过预实验①方法上：通过建立新算法，整合HiC、ChIP-seq数据，鉴定N-SIDE并通过免疫荧光染色验证；②功能上：通过表观修饰酶JMJD2复合物扰乱N-SIDE，显著影响干细胞多能性维持及神经分化；③机制上：JMJD2复合物在细胞命运决定中可从表观修饰、染色质三维结构层面对N-SIDE进行调控。前期我们鉴定出了N-SIDE，并证实N-SIDE在细胞命运决定中具有重要作用，并解析了部分机制。本项目将承前启后，对N-SIDE作进一步验证，并深层次解析N-SIDE调控细胞命运决定的功能和机理。

Epigenetic modification, 3D chromatin structure and nuclear spatial localization of genes are important to regulate gene expression and regulated by each other. The functions and mechanisms of how they work together to regulate gene expression remain largely unclear. In order to elucidate the phenomenon that 3D chromatin structure with specific epigenetic modification form nuclear nuclear spaticial domain during cell fate decision, we propose the concept of Nuclear Spatial Interacting Domains of Epigenome (N-SIDE). Our recent preliminary data showed that ① Method: defined N-SIDE with new algorithm integrating Hi-C and ChIP-seq data, and validated N-SIDE by immunofluorescence combined with super-resolution microscopy ; ② Function: disruption of N-SIDE, significantly affected the pluripotency maitenance and neural differentiation by manipulating JMJD2 complex; ③ Mechanism: The N-SIDE can be regulated by epigenetic modification, 3D chromatin structurelocalization through JMJD2 complex during cell fate decision. In conclusion, we defined N-SIDE and study its function and partial mechanism. Therefore, the project will further validate N-SIDE, and dissect the functions and mechanisms of N-SIDE in cell fate decision.