Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution
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Jaenisch_Tracing dynamic.pdf
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3.42 MB
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Author(s)
Stelzer, Yonatan
Soldner, Frank
Markoulaki, Styliani
Shivalila, Chikdu Shakti
Jaenisch, Rudolf
Date Issued
September 2015
Journal
Cell
Publisher
Elsevier
Citation
Stelzer, Yonatan et al. “Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution.” Cell 163.1 (2015): 218–229.
Version
Author's final manuscript
Abstract
Mammalian DNA methylation plays an essential role in development. To date, only snapshots of different mouse and human cell types have been generated, providing a static view on DNA methylation. To enable monitoring of methylation status as it changes over time, we establish a reporter of genomic methylation (RGM) that relies on a minimal imprinted gene promoter driving a fluorescent protein. We show that insertion of RGM proximal to promoter-associated CpG islands reports the gain or loss of DNA methylation. We further utilized RGM to report endogenous methylation dynamics of non-coding regulatory elements, such as the pluripotency-specific super enhancers of Sox2 and miR290. Loci-specific DNA methylation changes and their correlation with transcription were visualized during cell-state transition following differentiation of mouse embryonic stem cells and during reprogramming of somatic cells to pluripotency. RGM will allow the investigation of dynamic methylation changes during development and disease at single-cell resolution.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2015.08.046
