Effects of dppa3 on DNA methylation dynamics during primordial germ cell development in mice

Biol Reprod. 2013 May 23;88(5):125. doi: 10.1095/biolreprod.112.105932. Print 2013 May.

Abstract

DNA methylation is a central epigenetic event that regulates cellular differentiation, reprogramming, and pathogenesis. Genomewide DNA demethylation occurs in preimplantation embryos and in embryonic germ cell precursors called primordial germ cells (PGCs). We previously showed that Dppa3, also known as Stella and PGC7, protects the maternal genome from tet methylcytosine dioxygenase 3 (Tet3)-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in zygotes. Here, we demonstrated that retrotransposon genes, such as long interspersed nuclear element-1 (Line-1) and intracisternal A particle (IAP), showed higher 5mC levels in Dppa3-null PGCs. In contrast, oxidative bisulfite sequence analysis revealed that the amounts of 5hmC in Line-1 and IAP were slightly reduced in the Dppa3-deficient PGCs. From our findings, we propose that Dppa3 is involved in the Tet-mediated active demethylation process during reprogramming of PGCs.

Keywords: DNA demethylation; epigenetics; primordial germ cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone
  • DNA Methylation
  • Embryonic Development / genetics*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Developmental*
  • Genes, Intracisternal A-Particle / genetics
  • Germ Cells / metabolism*
  • Mice
  • Mice, Knockout
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • Dppa3 protein, mouse
  • ECAT11 protein, mouse
  • RNA-Binding Proteins
  • Repressor Proteins