PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions
PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions
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PCGF6 作为转录激活剂通过超级增强子依赖性染色质相互作用调节干细胞多能性
DOI：
10.1007/s13238-019-0629-9
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发表时间：
2019-10-01
期刊：
影响因子：
21.1
通讯作者：
Ding, Junjun
中科院分区：
文献类型：
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作者：
Huang, Xiaona;Wei, Chao;Ding, Junjun
多梳组（Polycomb group，PcG）环指蛋白6（Ring finger protein 6，PCGF 6）是转录抑制复合物PcG的一员，在调节多能性基因表达中也具有激活功能。然而，对PCGF 6激活功能的潜在机制知之甚少。在这里，我们发现PCGF 6与多能性因子如OCT 4共定位于基因激活区域沿着。此外，PCGF 6被OCT 4募集到细胞周期相关基因上游的超级增强子（SE）区域的子集，并增加其表达。通过结合启动子捕获Hi-C数据，我们发现PCGF 6通过3D染色质调节SE-启动子相互作用来激活细胞周期基因。我们的研究结果揭示了PcG蛋白调控多能性的新机制，为多能干细胞的治疗应用提供了研究基础。
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.