研究人员揭示了小鼠从胚胎第3.5天（E3.5）到E7.5天的SOX2结合情况。在E3.5内细胞团（ICM）中，SOX2调控ICM-滋养外胚层程序，但不需要打开全局增强子。相反，SOX2占用了部分由早期表达转录因子（TF）TFAP2C和NR5A2打开的预可及性增强子。
当细胞具有初始多能性和形成多能性时，SOX2会通过打开增强子或为将来的快速激活做好准备而广泛地重新分配。因此，多方面的先锋TF-增强子相互作用是胚胎多能性进展的基础，包括在E3.5 ICM中连接全能性和多能性的独特状态。
据了解，先锋TF，如OCT4和SOX2，在多能性调控中发挥着至关重要的作用。然而，核心TF管理的多能性调控回路主要是从培养细胞中推断出来的。
附：英文原文
Title: Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos
Author: Lijia Li, Fangnong Lai, Xiaoyu Hu, Bofeng Liu, Xukun Lu, Zili Lin, Ling Liu, Yunlong Xiang, Tristan Frum, Michael A. Halbisen, Fengling Chen, Qiang Fan, Amy Ralston, Wei Xie
Issue&Volume: 2023-12-15
Abstract: 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.
DOI: adi5516
Source: https://www.science.org/doi/10.1126/science.adi5516