Epigenetic reprogramming in the germline: towards the ground state of the epigenome

Abstract

Epigenetic reprogramming in the germline provides a developmental model to study the erasure of epigenetic memory as it occurs naturallyin vivoin the course of normal embryonic development. Our data show that germline reprogramming comprises both active DNA demethylation and extensive chromatin remodelling that are mechanistically linked through the activation of the base excision DNA repair pathway involved in the DNA demethylation process. The observed molecular hallmarks of the germline reprogramming exhibit intriguing similarities to other dedifferentiation or regeneration systems, pointing towards the existence of unifying molecular pathways underlying cell fate reversal. Elucidation of molecular processes involved in the resetting of epigenetic informationin vivowill thus add to our ability to manipulate cell fate and to restore pluripotency inin vitrosettings.