Title |
An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator
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Published in |
Nature Communications, December 2014
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DOI | 10.1038/ncomms6619 |
Pubmed ID | |
Authors |
Dong-Sung Lee, Jong-Yeon Shin, Peter D. Tonge, Mira C. Puri, Seungbok Lee, Hansoo Park, Won-Chul Lee, Samer M. I. Hussein, Thomas Bleazard, Ji-Young Yun, Jihye Kim, Mira Li, Nicole Cloonan, David Wood, Jennifer L. Clancy, Rowland Mosbergen, Jae-Hyuk Yi, Kap-Seok Yang, Hyungtae Kim, Hwanseok Rhee, Christine A. Wells, Thomas Preiss, Sean M. Grimmond, Ian M. Rogers, Andras Nagy, Jeong-Sun Seo |
Abstract |
Reprogramming of somatic cells to induced pluripotent stem cells involves a dynamic rearrangement of the epigenetic landscape. To characterize this epigenomic roadmap, we have performed MethylC-seq, ChIP-seq (H3K4/K27/K36me3) and RNA-Seq on samples taken at several time points during murine secondary reprogramming as part of Project Grandiose. We find that DNA methylation gain during reprogramming occurs gradually, while loss is achieved only at the ESC-like state. Binding sites of activated factors exhibit focal demethylation during reprogramming, while ESC-like pluripotent cells are distinguished by extension of demethylation to the wider neighbourhood. We observed that genes with CpG-rich promoters demonstrate stable low methylation and strong engagement of histone marks, whereas genes with CpG-poor promoters are safeguarded by methylation. Such DNA methylation-driven control is the key to the regulation of ESC-pluripotency genes, including Dppa4, Dppa5a and Esrrb. These results reveal the crucial role that DNA methylation plays as an epigenetic switch driving somatic cells to pluripotency. |
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Australia | 2 | 10% |
Spain | 2 | 10% |
France | 2 | 10% |
Canada | 1 | 5% |
Switzerland | 1 | 5% |
Unknown | 8 | 40% |
Demographic breakdown
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Members of the public | 14 | 70% |
Scientists | 6 | 30% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Brazil | 2 | <1% |
United States | 2 | <1% |
France | 1 | <1% |
Australia | 1 | <1% |
United Kingdom | 1 | <1% |
Switzerland | 1 | <1% |
Spain | 1 | <1% |
China | 1 | <1% |
Unknown | 256 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 69 | 26% |
Researcher | 63 | 24% |
Student > Master | 26 | 10% |
Student > Bachelor | 18 | 7% |
Professor | 17 | 6% |
Other | 43 | 16% |
Unknown | 30 | 11% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 108 | 41% |
Biochemistry, Genetics and Molecular Biology | 76 | 29% |
Medicine and Dentistry | 12 | 5% |
Engineering | 10 | 4% |
Computer Science | 6 | 2% |
Other | 24 | 9% |
Unknown | 30 | 11% |