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Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting.
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| Nature. (24) June 2004 |
| Sasaki Laboratory, Division of Human Genetics |
Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting.
Masahiro Kaneda, Masaki Okano, Kenichiro Hata, Takashi Sado, Naomi Tsujimoto, En Li & Hiroyuki Sasaki
Nature 429, 900-903, 2004
Imprinted genes are epigenetically marked during gametogenesis so that they are exclusively expressed from either the paternal or the maternal allele in offspring. Although de novo DNA methyltransferases of the Dnmt3 family are implicated in maternal imprinting, the lethality of Dnmt3a and Dnmt3b knockout mice has precluded further studies. We here disrupt Dnmt3a and Dnmt3b in germ cells, leaving them intact in somatic cells, by conditional knockout technology. Offspring from Dnmt3a conditional mutant females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined. Dnmt3a conditional mutant males show impaired spermatogenesis and lack methylation at two out of three paternally imprinted loci examined in spermatogonia. By contrast, Dnmt3b conditional mutants and their offspring show no apparent phenotype. These results indicate that Dnmt3a, but not Dnmt3b is required for methylation of most imprinted loci in germ cells.
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Cycle of genomic imprinting
Gamete-derived methylation patterns (imprints) of imprinted genes are maintained in somatic tissues throughout embryonic development (by the action of maintenance DNA methyltransferase Dnmt1 and its isoform Dnmt1o), but are erased in primordial germ cells and re-established during gametogenesis. Our study showed that Dnmt3a, in addition to Dnmt3L, is required for the re-establishment of imprints in male and female gametogenesis.
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Entrez PubMed |
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