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Primordial germ cell (PGC) development is characterized by global epigenetic remodeling, which resets genomic potential and establishes an epigenetic ground state. Here we recapitulate PGC specification in vitro from naive embryonic stem cells and characterize the early events of epigenetic reprogramming during the formation of the human and mouse germline. Following rapid de novo DNA methylation during priming to epiblast-like cells, methylation is globally erased in PGC-like cells. Repressive chromatin marks (H3K9me2/3) and transposable elements are enriched at demethylation-resistant regions, while active chromatin marks (H3K4me3 or H3K27ac) are more prominent at regions that demethylate faster. The dynamics of specification and epigenetic reprogramming show species-specific differences, in particular markedly slower reprogramming kinetics in the human germline. Differences in developmental kinetics may be explained by differential regulation of epigenetic modifiers. Our work establishes a robust and faithful experimental system of the early events of epigenetic reprogramming and regulation in the germline.

Original publication

DOI

10.1016/j.devcel.2016.09.015

Type

Journal article

Journal

Dev Cell

Publication Date

10/10/2016

Volume

39

Pages

104 - 115

Keywords

DNA methylation, PGC, PGC specification, PGC-like cell, Piwi-interacting RNA, chromatin, epigenetic reprogramming, epigenetic resetting, piRNA, primordial germ cell, Animals, Body Patterning, DNA Methylation, DNA Transposable Elements, Germ Cells, Human Embryonic Stem Cells, Humans, Mice, Mouse Embryonic Stem Cells, Transcription, Genetic