The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming

被引:31
作者
Cheng, Zhou-Li [1 ,2 ,3 ,4 ]
Zhang, Meng-Li [1 ,2 ,3 ,5 ]
Lin, Huai-Peng [6 ]
Gao, Chao [1 ,2 ,3 ,4 ]
Song, Jun-Bin [1 ,2 ,3 ,4 ]
Zheng, Zhihong [7 ,8 ]
Li, Linpeng [9 ]
Zhang, Yanan [10 ]
Shen, Xiaoqi [10 ]
Zhang, Hao [11 ]
Huang, Zhenghui [12 ]
Zhan, Wuqiang [1 ,2 ,3 ,4 ]
Zhang, Cheng [1 ,2 ,3 ,4 ]
Hu, Xu [13 ]
Sun, Yi-Ping [1 ,2 ,3 ,4 ]
Jiang, Lubing [12 ]
Sun, Lei [1 ,2 ,3 ,4 ]
Xu, Yanhui [1 ,2 ,3 ,4 ]
Yang, Chen [11 ]
Ge, Yuanlong [14 ]
Zhao, Yong [14 ]
Liu, Xingguo [9 ]
Yang, Hui [5 ]
Liu, Pengyuan [15 ,16 ]
Guo, Xing [10 ]
Guan, Kun-Liang [17 ,18 ]
Xiong, Yue [19 ]
Zhang, Mingliang [13 ]
Ye, Dan [1 ,2 ,3 ,4 ,20 ]
机构
[1] Fudan Univ, Huashan Hosp, Shanghai, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai Key Lab Med Epigenet, Cell Biol Lab, Shanghai, Peoples R China
[3] Minist Educ, Key Lab Metab & Mol, Shanghai, Peoples R China
[4] Minist Sci & Technol, Int Colab Med Epigenet & Metab, Beijing, Peoples R China
[5] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200040, Peoples R China
[6] Xiamen Univ, Med Coll, Xiamen 361102, Peoples R China
[7] Zhejiang Univ, Womens Hosp, Dept Gynecol Oncol, Hangzhou 310029, Zhejiang, Peoples R China
[8] Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou 310029, Zhejiang, Peoples R China
[9] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol,Guangdong Prov Key Lab Ste, Guangzhou 510530, Peoples R China
[10] Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Peoples R China
[11] Chinese Acad Sci, Inst Plant Physiol & Ecol, Shanghai Inst Biol Sci, Key Lab Synthet Biol, Shanghai 200032, Peoples R China
[12] Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai 200031, Peoples R China
[13] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Reprod Med, Dept Histoembryol Genet & Dev Biol, Shanghai, Peoples R China
[14] Sun Yat Sen Univ, Sch Life Sci, MOE Key Lab Gene Funct & Regulat, State Key Lab Biocontrol, Guangzhou 510006, Peoples R China
[15] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Resp Med, Hangzhou 310016, Zhejiang, Peoples R China
[16] Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou 310016, Zhejiang, Peoples R China
[17] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[18] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA
[19] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[20] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China
基金
浙江省自然科学基金; 国家重点研发计划;
关键词
TET PROTEINS; SCAN-DOMAIN; GENOMIC STABILITY; RECRUITS TET2; STEM-CELLS; IPS CELLS; 5-METHYLCYTOSINE; EXPRESSION; CONVERSION; DNA;
D O I
10.1016/j.celrep.2020.107877
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Evolutionarily conserved SCAN (named after SRE-ZBP, CTfin51, AW-1, and Number 18 cDNA)-domain-containing zinc finger transcription factors (ZSCAN) have been found in both mouse and human genomes. Zscan4 is transiently expressed during zygotic genome activation (ZGA) in preimplantation embryos and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control. Here, we show that Zscan4f, a representative of ZSCAN proteins, is able to recruit Tet2 through its SCAN domain. The Zscan4f-Tet2 interaction promotes DNA demethylation and regulates the expression of target genes, particularly those encoding glycolytic enzymes and proteasome subunits. Zscan4f regulates metabolic rewiring, enhances proteasome function, and ultimately promotes 1PSC generation. These results identify Zscan4f as an important partner of Tet2 in regulating target genes and promoting iPSC generation and suggest a possible and common mechanism shared by SCAN family transcription factors to recruit ten-eleven translocation (TET) DNA dioxygenases to regulate diverse cellular processes, including reprogramming.
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页数:19
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