DNA methylation remodeling in vitro and in vivo

In mammals, global DNA demethylation in vivo occurs in the pre-implantation embryo and in primordial germ cells (PGCs) where it is hypothesized to create a blank slate or 'tabula rasa' upon which new DNA methylation patterns are written. However, global DNA demethylation in vivo is far from complete with a small number of loci protected from demethylation. Failure to demethylate, or overt demethylation results in compromised differentiation. Recent work has shown that reversion of primed human pluripotent stem cells to the naïve state leads to unbridled DNA demethylation which has unknown consequences on the quality differentiated cells created in vitro. Taken together understanding DNA methylation remodeling is critical for understanding the epigenetic foundations of life, and the quality of stem cells for regenerative medicine.