Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos

• 成果类型: Article
• 署名作者: Li, Lijia; Lai, Fangnong; Hu, Xiaoyu; Liu, Bofeng; Lu, Xukun; Lin, Zili; Liu, Ling; Xiang, Yunlong; Frum, Tristan; Halbisen, Michael A.; Chen, Fengling; Fan, Qiang; Ralston, Amy; Xie, Wei
• 署名单位: Tsinghua University; Tsinghua University; Beijing University of Agriculture; Beijing University of Agriculture; Chongqing Medical University; Michigan State University; University of Michigan System; University of Michigan
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8391
• DOI: 10.1126/science.adi5516
• 发表日期: 2023-12-15
• 关键词: pioneer transcription factors; cell-fate; primitive endoderm; factor ap-2-gamma; stem-cells; rna-seq; mouse; gene; epiblast; sox2

摘要

Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then widely redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for rapid future activation. Hence, multifaceted pioneer TF-enhancer interaction underpins pluripotency progression in embryos, including a distinctive state in E3.5 ICM that bridges totipotency and pluripotency.