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

Lee, D.-S. et al. (2014) An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. Nature Communications, 5, (doi: 10.1038/ncomms6619) (PMID:25493341) (PMCID: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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wells, Dr Christine and Grimmond, Professor Sean
• 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., and Seo, J.-S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Nature Communications 5:5619
• Publisher Policy: Reproduced under a Creative Commons License