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 journalArticle

59 Citations (Scopus)

Abstract

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
JournalCell
Volume163
Issue number1
DOIs
StatePublished - Sep 24 2015
Externally publishedYes

Fingerprint

Methylation
DNA Methylation
CpG Islands
Transcription
Stem cells
Genes
Cells
Monitoring

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Stelzer, Y., Shivalila, C. S., Soldner, F., Markoulaki, S., & Jaenisch, R. (2015). Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution. Cell, 163(1), 218-229. https://doi.org/10.1016/j.cell.2015.08.046

Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution. / Stelzer, Yonatan; Shivalila, Chikdu Shakti; Soldner, Frank; Markoulaki, Styliani; Jaenisch, Rudolf.

In: Cell, Vol. 163, No. 1, 24.09.2015, p. 218-229.

Research output: Contribution to journalArticle

Stelzer, Y, Shivalila, CS, Soldner, F, Markoulaki, S & Jaenisch, R 2015, 'Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution', Cell, vol. 163, no. 1, pp. 218-229. https://doi.org/10.1016/j.cell.2015.08.046
Stelzer, Yonatan ; Shivalila, Chikdu Shakti ; Soldner, Frank ; Markoulaki, Styliani ; Jaenisch, Rudolf. / Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution. In: Cell. 2015 ; Vol. 163, No. 1. pp. 218-229.
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