Vitamin C modulates TET1 function during somatic cell reprogramming

被引：217

作者：

Chen, Jiekai ^{[1
,2
]}

Guo, Lin ^{[1
,2
]}

Zhang, Lei ^{[3
]}

Wu, Haoyu ^{[1
,4
]}

Yang, Jiaqi ^{[1
,2
]}

Liu, He ^{[1
,2
]}

Wang, Xiaoshan ^{[1
,2
]}

Hu, Xiao ^{[3
]}

Gu, Tianpeng ^{[3
]}

Zhou, Zhiwei ^{[1
,2
]}

Liu, Jing ^{[1
,2
]}

Liu, Jiadong ^{[1
,5
]}

Wu, Hongling ^{[1
,2
]}

Mao, Shi-Qing ^{[3
]}

Mo, Kunlun ^{[1
,2
]}

Li, Yingying ^{[1
,2
]}

Lai, Keyu ^{[1
,2
]}

Qi, Jing ^{[1
,2
]}

Yao, Hongjie ^{[1
,2
]}

Pan, Guangjin ^{[1
,2
]}

Xu, Guo-Liang ^{[3
]}

Pei, Duanqing ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Grp DNA Metab,State Key Lab Mol Biol, Shanghai, Peoples R China

[4] Jilin Univ, Coll Pharm, Dept Biol Engn, Changchun 130023, Peoples R China

[5] S China Univ Technol, Sch Biosci & Bioengn, Guangzhou, Guangdong, Peoples R China

来源：

NATURE GENETICS | 2013年 / 45卷 / 12期

基金：

中国国家自然科学基金;

关键词：

PLURIPOTENT STEM-CELLS; LARGE GENE LISTS; DNA DEMETHYLATION; MAMMALIAN DNA; MOUSE; 5-HYDROXYMETHYLCYTOSINE; GENERATION; 5-METHYLCYTOSINE; 5-CARBOXYLCYTOSINE; SPECIFICATION;

D O I：

10.1038/ng.2807

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs)(1) through the activity of histone demethylating dioxygenases(2,3). TET hydroxylases are also dioxygenases implicated in active DNA demethylation(4-8). Here we report that TET1 either positively or negatively regulates somatic cell reprogramming depending on the absence or presence of vitamin C. TET1 deficiency enhances reprogramming, and its overexpression impairs reprogramming in the context of vitamin C-2,C-9 by modulating the obligatory mesenchymal-to-epithelial transition (MET)(10,11). In the absence of vitamin C, TET1 promotes somatic cell reprogramming independent of MET. Consistently, TET1 regulates 5-hydroxymethylcytosine (5hmC) formation at loci critical for MET in a vitamin C-dependent fashion. Our findings suggest that vitamin C has a vital role in determining the biological outcome of TET1 function at the cellular level. Given its benefit to human health, vitamin C should be investigated further for its role in epigenetic regulation.

引用

页码：1504 / U140

页数：7

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