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.

DOI: 10.1016/j.molcel.2012.11.001

Extracted Key Phrases

Showing 1-10 of 19 references

Embryonic Stem Cells, ZFP57/KAP1 Recognize a Methylated Hexanucleotide to Affect Chromatin and DNA Methylation of Imprinting Control Regions

  • V Grimaldi, G Riccio
  • 2011
Showing 1-10 of 118 extracted citations
020040020132014201520162017
Citations per Year

1,006 Citations

Semantic Scholar estimates that this publication has received between 616 and 1,544 citations based on the available data.

See our FAQ for additional information.