title: Comparative Principles of DNA Methylation Reprogramming during Human and Mouse In Vitro Primordial Germ Cell Specification.
abstract: 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.
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK. Electronic address: vonmeyenn@babraham.ac.uk.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Meyenn
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Rebecca V
authors.initials: RV
authors.lastname: Berrens
authors.affiliation: Bioinformatics Group, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Andrews
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Fátima
authors.initials: F
authors.lastname: Santos
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Collier
authors.affiliation: Bioinformatics Group, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Krueger
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Osorno
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Dean
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rugg-Gunn
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. Electronic address: wolf.reik@babraham.ac.uk.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004251:DNA Transposable Elements
keywords: DNA methylation; PGC; PGC specification; PGC-like cell; Piwi-interacting RNA; chromatin; epigenetic reprogramming; epigenetic resetting; piRNA; primordial germ cell