Lee, Dong-Sung and Shin, Jong-Yeon and Tonge, Peter D and Puri, Mira C and Lee, Seungbok and Park, Hansoo and Lee, Won-Chul and Hussein, Samer M I and Bleazard, Thomas and Yun, Ji-Young and Kim, Jihye and Li, Mira and Cloonan, Nicole and Wood, David and Clancy, Jennifer L and Mosbergen, Rowland and Yi, Jae-Hyuk and Yang, Kap-Seok and Kim, Hyungtae and Rhee, Hwanseok and Wells, Christine A and Preiss, Thomas and Grimmond, Sean M and Rogers, Ian M and Nagy, Andras and Seo, Jeong-Sun (2014) An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. Nature Communications, 5. p. 5619. ISSN 2041-1723 (OA)
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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.
| Item Type: | Article |
|---|---|
| Keywords: | DOAJ Publication |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 Feb 2016 05:05 |
| Last Modified: | 18 May 2016 23:39 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/357 |
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