Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice.
Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice.
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DOI：
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发表时间：
2002-04
期刊：
影响因子：
4.6
通讯作者：
K. Hata;M. Okano;Hong Lei;E. Li
中科院分区：
文献类型：
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作者：
K. Hata;M. Okano;Hong Lei;E. Li
基因组印记是由父亲和母亲基因组的差异甲基化调节的。然而，它仍然是未知的，如何在配子发生过程中建立父母的印记。在这项研究中，我们证明，Dnmt 3L，与DNA甲基转移酶，Dnmt 3a和Dnmt 3b共享同源性，但缺乏酶活性的蛋白质，是必要的建立母亲的甲基化印记和适当表达的母亲印迹基因。我们还表明，Dnmt 3L与Dnmt 3a和Dnmt 3b相互作用，并在转染细胞的细胞核中与这些酶共定位，这表明Dnmt 3L可能通过Dnmt 3家族酶调节基因组印迹。与该模型一致，我们表明[Dnmt 3a（-/-），Dnmt 3b（+/-）]小鼠也未能建立母体甲基化印记。此外，Dnmt 3a和Dnmt 3L都是精子发生所必需的。总之，我们的研究结果表明，Dnmt 3L可能与Dnmt 3家族甲基转移酶合作，在卵母细胞中进行母体印记基因的从头甲基化。
Genomic imprinting is regulated by differential methylation of the paternal and maternal genome. However, it remains unknown how parental imprinting is established during gametogenesis. In this study, we demonstrate that Dnmt3L, a protein sharing homology with DNA methyltransferases, Dnmt3a and Dnmt3b, but lacking enzymatic activity, is essential for the establishment of maternal methylation imprints and appropriate expression of maternally imprinted genes. We also show that Dnmt3L interacts with Dnmt3a and Dnmt3b and co-localizes with these enzymes in the nuclei of transfected cells, suggesting that Dnmt3L may regulate genomic imprinting via the Dnmt3 family enzymes. Consistent with this model, we show that [Dnmt3a(-/-), Dnmt3b(+/-)] mice also fail to establish maternal methylation imprints. In addition, both Dnmt3a and Dnmt3L are required for spermatogenesis. Together, our findings suggest that Dnmt3L may cooperate with Dnmt3 family methyltransferases to carry out de novo methylation of maternally imprinted genes in oocytes.