DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages

Danielle M. Maatouk, Lori D. Kellam, Melissa R W Mann, Hong Lei, Li En, Marisa S. Bartolomei, James L. Resnick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

DNA methylation is necessary for the silencing of endogenous retrotransposons and the maintenance of monoallelic gene expression at imprinted loci and on the X chromosome. Dynamic changes in DNA methylation occur during the initial stages of primordial germ cell development; however, all consequences of this epigenetic reprogramming are not understood. DNA demethylation in postmigratory primordial germ cells coincides with erasure of genomic imprints and reactivation of the inactive X chromosome, as well as ongoing germ cell differentiation events. To investigate a possible role for DNA methylation changes in germ cell differentiation, we have studied several marker genes that initiate expression at this time. Here, we show that the postmigratory germ cell-specific genes Mvh, Dazl and Scp3 are demethylated in germ cells, but not in somatic cells. Premature loss of genomic methylation in Dnmt1 mutant embryos leads to early expression of these genes as well as GCNA1, a widely used germ cell marker. In addition, GCNA1 is ectopically expressed by somatic cells in Dnmt1 mutants. These results provide in vivo evidence that postmigratory germ cell-specific genes are silenced by DNA methylation in both premigratory germ cells and somatic cells. This is the first example of ectopic gene activation in Dnmt1 mutant mice and suggests that dynamic changes in DNA methylation regulate tissue-specific gene expression of a set of primordial germ cell-specific genes.

Original languageEnglish (US)
Pages (from-to)3411-3418
Number of pages8
JournalDevelopment
Volume133
Issue number17
DOIs
StatePublished - Sep 2006

Keywords

  • Mouse
  • Primordial germ cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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