An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator

Lee, Dong-Sung, Shin, Jong-Yeon, Tonge, Peter D., Puri, Mira C., Lee, Seungbok, Park, Hansoo, Lee, Won-Chul, Hussein, Samer M. I., Bleazard, Thomas, Yun, Ji-Young, Kim, Jihye, Li, Mira, Cloonan, Nicole, Wood, David, Clancy, Jennifer L., Mosbergen, Rowland, Yi, Jae-Hyuk, Yang, Kap-Seok, Kim, Hyungtae, Rhee, Hwanseok, Wells, Christine A., Preiss, Thomas, Grimmond, Sean M., Rogers, Ian M., Nagy, Andras and Seo, Jeong-Sun (2014) An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. Nature Communications, 5 5619.1-5619.10. doi:10.1038/ncomms6619

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Author Lee, Dong-Sung
Shin, Jong-Yeon
Tonge, Peter D.
Puri, Mira C.
Lee, Seungbok
Park, Hansoo
Lee, Won-Chul
Hussein, Samer M. I.
Bleazard, Thomas
Yun, Ji-Young
Kim, Jihye
Li, Mira
Cloonan, Nicole
Wood, David
Clancy, Jennifer L.
Mosbergen, Rowland
Yi, Jae-Hyuk
Yang, Kap-Seok
Kim, Hyungtae
Rhee, Hwanseok
Wells, Christine A.
Preiss, Thomas
Grimmond, Sean M.
Rogers, Ian M.
Nagy, Andras
Seo, Jeong-Sun
Title An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-12
Sub-type Article (original research)
DOI 10.1038/ncomms6619
Open Access Status DOI
Volume 5
Start page 5619.1
End page 5619.10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted 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
Keyword Embryonic Stem-Cells
Human Somatic-Cells
Defined Factors
Binding Sites
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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