Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution

Yonatan Stelzer, Chikdu Shakti Shivalila, Frank Soldner, Styliani Markoulaki, Rudolf Jaenisch

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


Summary 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.

Original languageEnglish (US)
Pages (from-to)218-229
Number of pages12
Issue number1
StatePublished - Sep 24 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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