An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator
AuthorLee, D-S; Shin, J-Y; Tonge, PD; Puri, MC; Lee, S; Park, H; Lee, W-C; Hussein, SMI; Bleazard, T; Yun, J-Y; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
AffiliationCentre for Cancer Research
School of Historical and Philosophical Studies
Anatomy and Neuroscience
Document TypeJournal Article
CitationsLee, D. -S., Shin, J. -Y., Tonge, P. D., Puri, M. C., Lee, S., Park, H., Lee, W. -C., Hussein, S. M. I., Bleazard, T., Yun, J. -Y., Kim, J., Li, M., Cloonan, N., Wood, D., Clancy, J. L., Mosbergen, R., Yi, J. -H., Yang, K. -S., Kim, H. ,... Seo, J. -S. (2014). An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. NATURE COMMUNICATIONS, 5 (1), https://doi.org/10.1038/ncomms6619.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284806
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.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References