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

研究成果: ジャーナルへの寄稿学術誌査読

999 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)900-903
ページ数4
ジャーナルNature
429
6994
DOI
出版ステータス出版済み - 6月 24 2004
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 一般

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