多个物种染色质三维空间结构的成功解析揭示其与转录调控、有丝分裂、细胞衰老等生物学过程密切相关。减数分裂前期同源重组过程高度保守且对遗传多样性意义重大，但此时期的染色质三维结构亟待解析。申请人已成功分离处于减数分裂同源重组时期的小鼠粗线期精母细胞和嗜热四膜虫新月期小核，并已通过高通量染色质构象捕获技术(Hi-C)获得后者的全基因组染色质相互作用图谱。在此基础上，本申请拟以两种进化上较远却又同时处于减数分裂同源重组时期的模型—哺乳动物小鼠粗线期精母细胞和原生动物嗜热四膜虫新月期小核为研究对象，利用Hi-C间接检测三维染色质构象和利用超高分辨率显微成像技术(STORM)直接观察染色质三维结构相结合，深度解析减数分裂同源重组时期染色质三维空间结构和活化/抑制等染色质表观遗传状态，从进化上研究其保守性和多样性。本项目对理解减数分裂同源重组时期的分子机制意义重大，并可为干预减数分裂相关疾病提供新策略。

The successful analyses of three-dimensional spatial chromatin structures in nuclei of multiple species revealed that high order chromatin organization is closely related with many key biological processes such as transcription regulation, mitosis, cellular senescence, etc. Homologous recombination during meiotic prophase is highly conserved and is of great significance for genetic diversity of gametes and progeny’s adaptability. However, the three-dimensional spatial chromatin structure during meiotic homologous recombination phase still remains as a mystery. The applicant’s group has successfully isolated pachytene spermatocytes of Mus musculus and crescent micronuclei of Tetrahymena thermophila, and also obtained genome-wide chromatin interaction map of crescent micronuclei of Tetrahymena thermophila through Hi-C, the genome-wide chromatin conformation capture method. Based on these preliminary data, the application will use these two model systems which are evolutionary far apart but both are during homologous recombination phases, to analysis three-dimensional spatial chromatin structure of meiotic homologous recombination phase of both mammal and protozoan, utilizing indirect method - (Hi-C) for capturing chromatin spatial conformation and direct method - super resolution imaging (STORM) for observing three-dimensional spatial chromatin structure, and the active or repressive epigenetic states of chromatin, in high resolution. We are also going to study the conservation and diversity of the three-dimensional spatial chromatin structure from evolutionary viewpoint. Our project is of great significance for understanding the molecular mechanism of meiotic homologous recombination, and may also provide new strategy into intervention of meiosis related diseases.