个人简介：

高亚威，同济大学生命科学与技术学院教授，博士生导师。主要从事发育和重编程的表观调控机制研究，解析早期胚胎中多种表观修饰重塑以及RNA表观修饰与核染色质的互作介导的转录调控机制。以第一或/和通讯作者（含共同）在Nature，Science，NCB，CSC等一流刊物上发表论文20余篇。成果曾获2016年度“中国生命科学十大进展”，三篇入选ESI高被引数据库。任SCLS青年编委，中国动物学会生殖生物学分会常务委员等，获国家自然科学二等奖（2/5），上海市自然科学一等奖（3/5），中国细胞生物学会干细胞分会“干细胞卓越青年研究员”（2023）等，动物学会第七届青年科技奖（2017）等。主持重点研发青年项目，国自然优青等项目，入选青拔、青托，启明星计划等人才项目。

报告摘要：

As the predominant components of the genome, retrotransposons play a critical role in mammalian genetic innovation and developmental processes regulation, especially for the genome activation during pre-implantation and extra-embryonic development. Over the past decade, we have utilized ultra-low-input multi-omics technologies to explore the epigenetic regulatory mechanisms underlying early embryo development and cell fate determinant. We found that the removal of H3K9me3 and DNA methylation contribute to activation of retrotransposons, especially long terminal repeats (LTRs), upon the reprogramming of fertilized embryos and somatic cell nuclear transfer (SCNT) embryos in mice. We further observed the histone chaperone CAF-1 responded rebuilding of H3K9me3 on LTRs since the 8-cell stage involve in the LTR transcriptional repression and subsequent heterochromatin formation. Additionally, we discovered that the L1 scaffold complex may facilitate KAP1 recruitment and establishment of H3K9me3 on 2C-repeats through RNA m6A and reader protein YTHDC1, promoting the exist of totipotency in embryo and embryonic stem cells. In subsequent work, we defined FTO and METTL16 as the L1 RNA m6A demethylase and writer protein respectively. We found the METTL16 sensitive m6A on structured L1 RNA is crucial for L1 scaffolding function and therefore indispensable for the silence of MERVL and exit from totipotency in mice. Remarkably, these regulatory model on retrotransposons evolutionary conserved in human embryonic development and pluripotency regulation. In human pre-implantation embryos, stage-specific H3K9me3 occupancy were defended on different LTR subfamilies to ensure retrotransposon silencing. Remarkably, we found the primate-specific L1PA utilizes RNA m6A modification in human embryonic stem cells to regulate epigenetic microenvironments and transcriptional activity on 8C-LTRs, governing pluripotency exit. Our study reveals the complex regulatory mechanisms of transposons in mammalian embryonic development, providing insights into transposon-mediated chromatin regulation and the molecular paradigms of species evolution.