From Germline to Soma: Epigenetic Dynamics in the Mouse Preimplantation Embryo

When reflecting about cell fate commitment we think of differentiation. Be it during embryonic development or in an adult stem cell niche, where cells of a higher potency specialize and cell fate decisions are taken. Under normal circumstances this process is definitive and irreversible. Cell fate commitment is achieved by the establishment of cell-type-specific transcriptional programmes, which in turn are guided, reinforced, and ultimately locked-in by epigenetic mechanisms. Yet, this plunging drift in cellular potency linked to epigenetically restricted access to genomic information is problematic for reproduction. Particularly in mammals where germ cells are not set aside early on like in other species. Instead they are rederived from the embryonic ectoderm, a differentiating embryonic tissue with somatic epigenetic features. The epigenomes of germ cell precursors are efficiently reprogrammed against the differentiation trend, only to specialize once more into highly differentiated, sex-specific gametes: oocyte and sperm. Their differentiation state is reflected in their specialized epigenomes, and erasure of these features is required to enable the acquisition of the totipotent cell fate to kick start embryonic development of the next generation. Recent technological advances have enabled unprecedented insights into the epigenetic dynamics, first of DNA methylation and then of histone modifications, greatly expanding the historically technically limited understanding of this processes. In this chapter we will focus on the details of embryonic epigenetic reprogramming, a cell fate determination process against the tide to a higher potency.