Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting

Masahiro Kaneda, Masaki Okano, Kenichiro Hata, Takashi Sado, Haomi Tsujimoto, En Li, Hiroyuki Sasaki

Research output: Contribution to journalArticle

831 Citations (Scopus)

Abstract

Imprinted genes are epigenetically marked during gametogenesis so that they are exclusively expressed from either the paternal or the maternal allele in offspring. Imprinting prevents parthenogenesis in mammals and is often disrupted in congenital malformation syndromes, tumours and cloned animals. 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 report the disruption of Dnmt3a and Dnmt3b in germ cells, with their preservation 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 of three paternally imprinted loci examined in spermatogonia. By contrast, Dnmt3b conditional mutants and their offspring show no apparent phenotype. The phenotype of Dnmt3a conditional mutants is indistinguishable from that of Dnmt3L knockout mice, except for the discrepancy in methylation at one locus. These results indicate that both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factors.

Original languageEnglish
Pages (from-to)900-903
Number of pages4
JournalNature
Volume429
Issue number6994
DOIs
Publication statusPublished - Jun 24 2004
Externally publishedYes

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Methyltransferases
Methylation
Mothers
DNA
Knockout Mice
Germ Cells
Alleles
Parthenogenesis
Gametogenesis
Phenotype
Spermatogonia
Spermatogenesis
Mammals
Technology
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. / Kaneda, Masahiro; Okano, Masaki; Hata, Kenichiro; Sado, Takashi; Tsujimoto, Haomi; Li, En; Sasaki, Hiroyuki.

In: Nature, Vol. 429, No. 6994, 24.06.2004, p. 900-903.

Research output: Contribution to journalArticle

Kaneda, M, Okano, M, Hata, K, Sado, T, Tsujimoto, H, Li, E & Sasaki, H 2004, 'Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting', Nature, vol. 429, no. 6994, pp. 900-903. https://doi.org/10.1038/nature02633
Kaneda M, Okano M, Hata K, Sado T, Tsujimoto H, Li E et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 2004 Jun 24;429(6994):900-903. https://doi.org/10.1038/nature02633
Kaneda, Masahiro ; Okano, Masaki ; Hata, Kenichiro ; Sado, Takashi ; Tsujimoto, Haomi ; Li, En ; Sasaki, Hiroyuki. / Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. In: Nature. 2004 ; Vol. 429, No. 6994. pp. 900-903.
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