Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2023-12-15 DOI:10.1126/science.adi5516

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

引用次数: 0

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.

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SOX2 与染色质的多方面相互作用是早期胚胎多能性进展的基础

先锋转录因子（TF），如 OCT4 和 SOX2，在多能性调控中发挥着至关重要的作用。然而，主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。在这项工作中，我们研究了小鼠从胚胎第 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-前胚层程序，但不需要打开全局增强子。相反，SOX2 会占据部分由早期表达 TF TFAP2C 和 NR5A2 打开的可进入的增强子。当细胞具有幼稚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，多方面的先驱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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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