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The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells

Authors
Journal
Molecular Cell
1097-2765
Publisher
Elsevier
Publication Date
Volume
48
Issue
6
Identifiers
DOI: 10.1016/j.molcel.2012.11.001
Disciplines
  • Biology
  • Computer Science

Abstract

Summary 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.

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