Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution

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 me...

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Bibliographic Details
Main Authors: Stelzer, Yonatan (Author), Soldner, Frank (Author), Markoulaki, Styliani (Author), Shivalila, Chikdu Shakti (Contributor), Jaenisch, Rudolf (Contributor)
Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor)
Format: Article
Language:English
Published: Elsevier, 2017-05-11T16:14:03Z.
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Online Access:Get fulltext
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100 1 0 |a Stelzer, Yonatan  |e author 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
100 1 0 |a Whitehead Institute for Biomedical Research  |e contributor 
100 1 0 |a Shivalila, Chikdu Shakti  |e contributor 
100 1 0 |a Jaenisch, Rudolf  |e contributor 
700 1 0 |a Soldner, Frank  |e author 
700 1 0 |a Markoulaki, Styliani  |e author 
700 1 0 |a Shivalila, Chikdu Shakti  |e author 
700 1 0 |a Jaenisch, Rudolf  |e author 
245 0 0 |a Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution 
260 |b Elsevier,   |c 2017-05-11T16:14:03Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/108812 
520 |a 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. 
520 |a National Institutes of Health (U.S.) (Grant HD 045022) 
546 |a en_US 
655 7 |a Article 
773 |t Cell