title: The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells.
abstract: Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global loss of methylation takes place during PGC expansion and migration with evidence for passive demethylation, but sequences that carry long-term epigenetic memory (imprints, CpG islands on the X chromosome, germline-specific genes) only become demethylated upon entry of PGCs into the gonads. The transcriptional profile of PGCs is tightly controlled despite global hypomethylation, with transient expression of the pluripotency network, suggesting that reprogramming and pluripotency are inextricably linked. Our results provide a framework for the understanding of the epigenetic ground state of pluripotency in the germline.
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Seisenberger
authors.forename: Simon
authors.initials: S
authors.lastname: Andrews
authors.forename: Felix
authors.initials: F
authors.lastname: Krueger
authors.forename: Julia
authors.initials: J
authors.lastname: Arand
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
authors.forename: Fátima
authors.initials: F
authors.lastname: Santos
authors.forename: Christian
authors.initials: C
authors.lastname: Popp
authors.forename: Bernard
authors.initials: B
authors.lastname: Thienpont
authors.forename: Wendy
authors.initials: W
authors.lastname: Dean
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D016678:Genome; D018392:Genomic Imprinting; D005854:Germ Cells / Q000378:metabolism*; D005855:Germ Layers / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D059467:Transcriptome; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism