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
1 RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China;
2 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China;
3 Department of Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China;
4 Program in Stem Cell and Regenerative Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China;
5 Center for Bioinformatics, School of Life Sciences, Peking University, Beijing 100871, China;
6 Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China;
7 Department of Histology and Embryology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
Funds: This research was funded by grants from the National Key Research and Development Program (2017YFA0102800 and 2016YFA[0101700]), the National Natural Science Foundation of China (Grant Nos. 31771639 and 81703086), the Guangdong Regenerative Medicine and Health of Guangdong Laboratory Frontier Exploration Project (2018GZR110105007), the Guangdong Innovative and Entrepreneurial Research Team Program 2016ZT06S029, the Fundamental Research Funds for the Central Universities (17ykzd04), Thousand Youth Talents Plan to J. Ding, and a project funded by China Postdoctoral Science Foundation (2017M622863) to F.L.
Received Date: 2019-01-18
Rev Recd Date:2019-04-15
Abstract
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.Keywords: PCGF6,
Polycomb group,
super-enhancer,
3D chromatin,
pluripotency
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