Replacement of Oct4 by Tet1 during iPSC Induction Reveals an Important Role of DNA Methylation and Hydroxymethylation in Reprogramming

被引：296

作者：

Gao, Yawei ^{[1
,2
]}

Chen, Jiayu ^{[1
,2
]}

Li, Ke ^{[2
]}

Wu, Tong ^{[2
]}

Huang, Bo ^{[2
]}

Liu, Wenqiang ^{[2
]}

Kou, Xiaochen ^{[2
]}

Zhang, Yu ^{[2
]}

Huang, Hua ^{[3
]}

Jiang, Yonghua ^{[2
]}

Yao, Chao ^{[2
]}

Liu, Xiaolei ^{[2
]}

Lu, Zhiwei ^{[2
]}

Xu, Zijian ^{[2
]}

Kang, Lan ^{[2
]}

Chen, Jun ^{[2
]}

Wang, Hailin ^{[3
]}

Cai, Tao ^{[2
]}

Gao, Shaorong ^{[1
,2
]}

机构：

[1] Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China

[2] Natl Inst Biol Sci, Beijing 102206, Peoples R China

[3] Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Res Ctr Ecoenvironm Sci, Beijing 100085, Peoples R China

来源：

CELL STEM CELL | 2013年 / 12卷 / 04期

关键词：

PLURIPOTENT STEM-CELLS; SOMATIC-CELLS; GENE-EXPRESSION; 5-HYDROXYMETHYLCYTOSINE; MOUSE; GENOME; 5-METHYLCYTOSINE; FIBROBLASTS; MICE; REGULATORS;

D O I：

10.1016/j.stem.2013.02.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

DNA methylation and demethylation have been proposed to play an important role in somatic cell reprogramming. Here, we demonstrate that the DNA hydroxylase Tet1 facilitates pluripotent stem cell induction by promoting Oct4 demethylation and reactivation. Moreover, Tet1 (T) can replace Oct4 and initiate somatic cell reprogramming in conjunction with Sox2 (S), Klf4 (K), and c-Myc (M). We established an efficient TSKM secondary reprogramming system and used it to characterize the dynamic profiles of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and gene expression during reprogramming. Our analysis revealed that both 5mC and 5hmC modifications increased at an intermediate stage of the process, correlating with a transition in the transcriptional profile. We also found that 5hmC enrichment is involved in the demethylation and reactivation of genes and regulatory regions that are important for pluripotency. Our data indicate that changes in DNA methylation and hydroxymethylation play important roles in genome-wide epigenetic remodeling during reprogramming.

引用

页码：453 / 469

页数：17

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