DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.
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.
Maatouk
Danielle M
DM
Department of Molecular Genetics and Microbiology, PO Box 100266, University of Florida, Gainesville, FL 32610-0266, USA.
Kellam
Lori D
LD
Mann
Mellissa R W
MR
Lei
Hong
H
Li
En
E
Bartolomei
Marisa S
MS
Resnick
James L
JL
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D020868:Gene Silencing; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014566:Urogenital System / Q000196:embryology; D014960:X Chromosome
D017931:DNA Primers; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse