Tracing dynamic changes of DNA methylation at single cell resolution
Open accessAbstract
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.
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RGM was used to monitor the DNA methylation status of non-coding regulatory elements during different biological processes, such as cellular reprogramming, tracking the enhancers associated with Sox2 and miR290.
“RGM was used to monitor the DNA methylation status of non-coding regulatory elements during different biological processes, such as cellular reprogramming, tracking the enhancers associated with Sox2 and miR290.”
From Mapping gene regulatory networks from single-cell omics data (2018) · cites this paper as [74]
Stelzer et al. established a reporter of genomic methylation (RGM) allowing real-time tracking of changes in DNA methylation at a specific locus, both in vitro and in vivo, with single-cell resolution.
“Stelzer et al. [74] established a reporter of genomic methylation (RGM), allowing real-time tracking of changes in DNA methylation at a specific locus, both in vitro and in vivo, with single-cell resolution.”
From Mapping gene regulatory networks from single-cell omics data (2018) · cites this paper as [74]
De-methylation of both the Sox2 and miR290 enhancers is a late event in the reprogramming process.
“They show that de-methylation of both these enhancers is a late event in the reprogramming process.”
From Mapping gene regulatory networks from single-cell omics data (2018) · cites this paper as [74]
A fluorescent in vivo reporter of genomic methylation enables microscopic examination of 5mC status at a single genomic locus with cellular resolution.
“In addition to sequencing-based single-cell methylome strategies, a fluorescent in vivo reporter of genomic methylation (RGM) enables microscopic examination of the 5mC status at a single genomic locus with cellular resolution (53).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [53]
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- Authors
- Stelzer, Y., Shivalila, C. S., Soldner, F., Markoulaki, S., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Jaenisch, Rudolf
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 163
- Issue
- 1
- Pages
- 218-229
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4583717
- OpenAlex
- W2105893097
- Cited by
- 141
- References
- 44
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 5 · 2022: 12 · 2021: 15 · 2020: 14 · 2019: 13 · 2018: 18 · 2017: 23 · 2016: 15 · 2015: 1 · 2014: 1
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD045022, HD045022, R37HD045022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation dynamics, fluorescent protein reporter, CpG islands, super-enhancers, SOX2, mouse embryonic stem cells, cell differentiation, somatic cell reprogramming, pluripotency, non-coding regulatory elements, transcription
- MeSH terms
- Animals, Enhancer Elements, Genetic, Humans, Promoter Regions, Genetic, DNA Modification Methylases, CpG Islands, DNA Methylation, MicroRNAs, Mice, Embryonic Stem Cells, SOXB1 Transcription Factors, Single-Cell Analysis
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