Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice
Author:
Hata Kenichiro, Okano Masaki, Lei Hong, Li En1
Affiliation:
1. Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
Abstract
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.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference45 articles.
1. Aapola, U., Kawasaki, K., Scott, H. S., Ollila, J., Vihinen, M., Heino, M., Shintani, A., Minoshima, S., Krohn, K., Antonarakis, S. E., Shimizu, N., Kudoh, J. and Peterson, P. (2000). Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family. Genomics65, 293-298. 2. Bachman, K. E., Rountree, M. R. and Baylin, S. B. (2001). Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J. Biol. Chem.276, 32282-32287. 3. Barlow, D. P. (1995) Gametic imprinting in mammals. Science270,1610-1613. 4. Barton, S. C., Surani, M. A. and Norris, M. L. (1984). Role of paternal and maternal genomes in mouse development. Nature311, 374-376. 5. Bird, A. P. and Wolffe, A. P. (1999). Methylation-induced repression–belts, braces, and chromatin. Cell99, 451-454.
Cited by
473 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|