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

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    Author
    Lee, D-S; Shin, J-Y; Tonge, PD; Puri, MC; Lee, S; Park, H; Lee, W-C; Hussein, SMI; Bleazard, T; Yun, J-Y; ...
    Date
    2014-12-01
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Grimmond, Sean; Mosbergen, Rowland; Wells, Christine
    Affiliation
    Centre for Cancer Research
    School of Historical and Philosophical Studies
    Anatomy and Neuroscience
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    Document Type
    Journal Article
    Citations
    Lee, 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 Status
    Open Access
    URI
    http://hdl.handle.net/11343/258237
    DOI
    10.1038/ncomms6619
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284806
    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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