YY1 Positively Regulates Transcription by Targeting Promoters and Super-Enhancers through the BAF Complex in Embryonic Stem Cells

YY1 通过 BAF 复合物靶向启动子和超增强子来正向调控胚胎干细胞中的转录

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作者:Jia Wang, Xingui Wu, Chao Wei, Xin Huang, Qian Ma, Xiaona Huang, Francesco Faiola, Diana Guallar, Miguel Fidalgo, Tingyuan Huang, Di Peng, Li Chen, Haopeng Yu, Xingyu Li, Junyi Sun, Xinyi Liu, Xiaoxia Cai, Xiao Chen, Ling Wang, Jian Ren, Jianlong Wang, Junjun Ding

Abstract

Yin Yang 1 (YY1) regulates early embryogenesis and adult tissue formation. However, the role of YY1 in stem cell regulation remains unclear. YY1 has a Polycomb group (PcG) protein-dependent role in mammalian cells. The PcG-independent functions of YY1 are also reported, although their underlying mechanism is still undefined. This paper reports the role of YY1 and BAF complex in the OCT4-mediated pluripotency network in mouse embryonic stem cells (mESCs). The interaction between YY1 and BAF complex promotes mESC proliferation and pluripotency. Knockdown of Yy1 or Smarca4, the core component of the BAF complex, downregulates pluripotency markers and upregulates several differentiation markers. Moreover, YY1 enriches at both promoter and super-enhancer regions to stimulate transcription. Thus, this study elucidates the role of YY1 in regulating pluripotency through its interaction with OCT4 and the BAF complex and the role of BAF complex in integrating YY1 into the core pluripotency network.

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