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18.07.18 Genome-scale oscillations in DNA methylation as cells undergo fate decisions

last modified Jul 18, 2018 09:41 PM
The Simons lab with colleagues from the Babraham Institute combined single-cell sequencing and biophysical modelling to follow DNA methylation states as cells begin to differentiate
18.07.18 Genome-scale oscillations in DNA methylation as cells undergo fate decisions

Co-expression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in methylation.

Genome-scale oscillations in DNA methylation during exit from pluripotency

Rulands S et al. (2018) Cell Systems (Online ahead of final publication.) DOI: 10.1016/j.cels.2018.06.012

 

Abstract from the paper

Pluripotency is accompanied by the erasure of parental epigenetic memory with naïve pluripotent cells exhibiting global DNA hypomethylation both in vitro and in vivo. Exit from pluripotency and priming for differentiation into somatic lineages is associated with genome-wide de novo DNA methylation.

We show that during this phase, co-expression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in this epigenetic mark. Using a combination of single-cell sequencing and quantitative biophysical modelling, we show that this variability is associated with coherent, genome-scale, oscillations in DNA methylation with an amplitude dependent on CpG density. Analysis of parallel single-cell transcriptional and epigenetic profiling provides evidence for oscillatory dynamics both in vitro and in vivo.

These observations provide insights into the emergence of epigenetic heterogeneity during early embryo development, indicating that dynamic changes in DNA methylation might influence early cell fate decisions.

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Read more about research in the Simons lab.

Watch Ben Simons describe his work in this short video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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