Abstract

Epigenetic mechanisms act to define and restrict cellular identity. In mammals, primordial germ cells (PGC), the precursors to sperm and oocytes, undergo unprecedented reprogramming including global erasure of DNA methylation and genomic imprints. This process resets the epigenome to enable the acquisition of totipotency – the capacity to form all cell types – in the zygote. We have been investigating the mechanism that drives comprehensive epigenome resetting in PGCs and find a key role for TET -mediated 5-hydroxymethylation. We also find rare loci that escape from epigenetic reprogramming in PGCs. The epigenetic states at these genomic sites may represent a mechanism for transgenerational epigenetic inheritance, which may be sensitive to environmental perturbations