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Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice

EMBO J. 2013 Feb 6;32(3):340-53. doi: 10.1038/emboj.2012.331. Epub 2012 Dec 14.

Abstract

Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs) is a critical first step to creating a totipotent epigenome in the germ line. We show here that, contrary to the prevailing model emphasizing active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner largely consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid cycling with little de novo or maintenance DNA methylation potential and no apparent major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins
  • Cell Cycle / physiology
  • Cell Proliferation
  • Chromatin / physiology
  • DNA Methylation / genetics
  • DNA Methylation / physiology*
  • DNA Primers / genetics
  • DNA Replication / physiology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Genome / genetics*
  • Genomic Imprinting / genetics*
  • Germ Cells / physiology*
  • Green Fluorescent Proteins
  • Kinetics
  • Mice
  • Microarray Analysis
  • Models, Biological*
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Repressor Proteins / metabolism
  • Sequence Analysis, DNA
  • Ubiquitin-Protein Ligases

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Chromatin
  • DNA Primers
  • Dmap1 protein, mouse
  • Nuclear Proteins
  • Repressor Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Ubiquitin-Protein Ligases
  • Uhrf1 protein, mouse