Unknown,Transcriptomics,Genomics,Proteomics

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Tet and TDG Mediate DNA Demethylation Essential for MET in Somatic Cell Reprogramming


ABSTRACT: Tet-mediated DNA oxidation is a new type of epigenetic modification in mammals and its role in the regulation of cell fate transition remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capability to be reprogrammed into iPS cells. We demonstrate that these Tet-deficient MEFs cannot be reprogrammed due to a blockage in the mesenchymal-to-epithelial transition (MET). Reprogramming of MEFs deficient in TDG is similarly blocked. The blockage is caused by impaired activation of crucial microRNAs, which depends on oxidative demethylation promoted by Tet and TDG. Reintroduction of either miR-200c or catalytically active Tet and TDG restores reprogramming to the respective knockout MEFs. Thus, oxidative demethylation is essential for somatic cell reprogramming. These findings provide mechanistic insights into the operation of epigenetic barriers in cell lineage conversion. Reduced Representation Bisulfite (RRBS, MspI,~75-400bp size fraction) and Tet-Assisted RRBS (TARRBS) of MEFs & reprogramming MEFs at Day 5

ORGANISM(S): Mus musculus

SUBMITTER: Shiqing Mao 

PROVIDER: E-GEOD-52741 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming.

Hu Xiao X   Zhang Lei L   Mao Shi-Qing SQ   Li Zheng Z   Chen Jiekai J   Zhang Run-Rui RR   Wu Hai-Ping HP   Gao Juan J   Guo Fan F   Liu Wei W   Xu Gui-Fang GF   Dai Hai-Qiang HQ   Shi Yujiang Geno YG   Li Xianlong X   Hu Boqiang B   Tang Fuchou F   Pei Duanqing D   Xu Guo-Liang GL  

Cell stem cell 20140213 4


Tet-mediated DNA oxidation is a recently identified mammalian epigenetic modification, and its functional role in cell-fate transitions remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capacity for reprogramming into induced pluripotent stem cells (iPSCs). We show that Tet-deficient MEFs cannot be reprogrammed because of a block in the mesenchymal-to-epithelial transition (MET) step. Reprogramming of MEFs deficient in  ...[more]

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