Early development

DNA methylation dynamics in pre- and post-implantation development

Top: Preimplanation and postimplantation timepoints with brightfield images and a schematic illustration. Hours and days post fertilization are indicated.
Bottom: Simplified schematic illustration of the DNA methylation dynamics during the preimplantation stages over selected genomic features.

Our group has developed and applied several genome-scale and other approaches to better understand the complete dynamic range of DNA methylation, at the nucleotide level and across organismal life, from zygote through adult lineages, refining decades old models of its regulatory contributions at every developmental stage.

Further reading:

Smith et al., Nature 2012
Smith et al., Nature 2014
Smith and Meissner, Nature Reviews Genetics 2013

Transition from DNA methylation independence to dependence

Schematic indicating the transition/switch to DNA methylation dependence from naïve to primed cells. Brightfield images on the right show human ES cells over 9 days in the absence of the maintenance methyltransferase DNMT1.

Preimplantation development represents a unique regulatory phase where cells are apparently not dependent on global DNA methylation. Through an unknown mechanism cells become sensitive to the loss of DNA methylation and even human ES cells under classic culture conditions undergo cell death in the absence of DNA methylation.

Further reading:

Liao et al., Nature Genetics 2015
Smith and Meissner, Nature Reviews Genetics 2013

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