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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, Seo, Jeong-Sun·2014·Nature Communications
DOI 10.1038/ncomms6619PMC PMC4284806
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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.

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Crossref · 10.1038/ncomms6619

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  • DNA methylation during iPS cell reprogramming facilitates chromatin remodeling while silencing differentiation-associated genes.

    “DNA methylation during iPS cell reprogramming facilitates chromatin remodeling while silencing differentiation-associated genes 90,91 .”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [90]

    The Abstract states that DNA methylation has been proposed to silence differentiation-associated genes while facilitating chromatin remodelling. The Results and Discussion section describes methylation as a modulator of histone changes, but the citing sentence presents the full proposed mechanism as an established fact. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Citations

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Research works printed but not linked: 35

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Metadata

Authors
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., Rhee, H., Wells, C. A., Preiss, T., Grimmond, S. M., Rogers, I. M., Nagy, A., & Seo, J.-S.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2014-12-10
Volume
5
Issue
1
ISSN
2041-1723
DOI
10.1038/ncomms6619
PMC
PMC4284806
Cited by
113
References
2
Language
en
Licence

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