PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions

PCGF6 通过超增强子依赖的染色质相互作用作为转录激活剂调节干细胞多能性

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作者:Xiaona Huang, Chao Wei, Fenjie Li, Lumeng Jia, Pengguihang Zeng, Jiahe Li, Jin Tan, Tuanfeng Sun, Shaoshuai Jiang, Jia Wang, Xiuxiao Tang, Qingquan Zhao, Bin Liu, Limin Rong, Cheng Li, Junjun Ding

Abstract

Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4. In addition, PCGF6 was recruited to a subset of the super-enhancer (SE) regions upstream of cell cycle-associated genes by OCT4, and increased their expression. By combining with promoter capture Hi-C data, we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin. Our findings highlight a novel mechanism of PcG protein in regulating pluripotency, and provide a research basis for the therapeutic application of pluripotent stem cells.

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