Coordinate regulation of DNA methyltransferase expression during oogenesis.
BACKGROUND
Normal mammalian development requires the action of DNA methyltransferases (DNMTs) for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA methylation, Dnmt3L, in isolated female germ cells.


RESULTS
Our results indicate that these enzymes are coordinately regulated and that their expression peaks during the stage of postnatal oocyte development when maternal methylation imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L deficient 15 dpp oocytes have aberrantly methylated Snrpn, Peg3 and Igf2r DMRs, but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ cell specific role for DNMT3L in the establishment of DNA methylation at repeat elements. Finally, real-time RT-PCR analysis indicates that the depletion of either DNMT3L or DNMT1o in growing oocytes results in the increased expression of the de novo methyltransferase Dnmt3b, suggesting a potential compensation mechanism by this enzyme for the loss of one of the other DNA methyltransferases.


CONCLUSIONS
Together these results provide a better understanding of the developmental regulation of Dnmt3a, Dnmt3b and Dnmt3L at the time of de novo methylation during oogenesis and demonstrate that the involvement of DNMT3L in retrotransposon silencing is restricted to the male germ line. This in turn suggests the existence of other factors in the oocyte that direct DNA methylation to transposons.
Lucifero
Diana
D
Montreal Children's Hospital Research Institute and Department of Pediatrics, McGill University, Montreal, Quebec, Canada. diana.lucifero@bbsrc.ac.uk <diana.lucifero@bbsrc.ac.uk>
La Salle
Sophie
S
Bourc'his
Déborah
D
Martel
Josée
J
Bestor
Timothy H
TH
Trasler
Jacquetta M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology* / Q000254:growth & development; D009866:Oogenesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000715535:Dnmt3a protein, mouse; C498796:Dnmt3l protein, mouse