QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Hirasawa, R. Articles by Sasaki, H. PubMed PubMed Citation Articles by Hirasawa, R. Articles by Sasaki, H. Related Content Related Article Social Bookmarking                   What's this?

Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development

¹ Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima 411-8540, Japan; ² Department of Genetics, School of Life Science, The Graduate University for Advanced Studies, Mishima 411-8540, Japan; ³ Reproductive Biology and Technology Research Team, National Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, Tsukuba 305-0901, Japan; ⁴ Laboratory of Epigenetics, Division of Protein Chemistry, Institute for Protein Research, Osaka University, Suita 565-0871, Japan; ⁵ Epigenetics Program, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA; ⁶ Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA

Parental origin-specific DNA methylation regulates the monoallelic expression of the mammalian imprinted genes. The methylation marks or imprints are established in the parental germline and maintained throughout embryonic development. However, it is unclear how the methylation imprints are maintained through extensive demethylation in cleavage-stage preimplantation embryos. Previous reports suggested that DNA methyltransferase(s) other than Dnmt1 is involved in the maintenance of the imprints during cleavage. Here we demonstrate, by using conditional knockout mice, that the other known DNA methyltransferases Dnmt3a and Dnmt3b are dispensable for the maintenance of the methylation marks at most imprinted loci. We further demonstrate that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of all imprinted loci examined in blastocysts. Consistent with these results we find that zygotic Dnmt1 is expressed in the preimplantation embryo. Thus, contrary to the previous reports, Dnmt1 alone is sufficient to maintain the methylation marks of the imprinted genes.

[Keywords: Genomic imprinting; DNA methylation; preimplantation embryos; Dnmt1]

Received February 25, 2008; revised version accepted April 14, 2008.

⁸ Corresponding author.

E-MAIL hisasaki{at}lab.nig.ac.jp; FAX 81-559-81-6800.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1667008.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Safeguarding parental identity: Dnmt1 maintains imprints during epigenetic reprogramming in early embryogenesis

Miguel R. Branco, Masaaki Oda, and Wolf Reik
Genes & Dev. 2008 22: 1567-1571. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				M. R. Branco, M. Oda, and W. Reik Safeguarding parental identity: Dnmt1 maintains imprints during epigenetic reprogramming in early embryogenesis Genes & Dev., June 15, 2008; 22(12): 1567 - 1571. [Abstract] [Full Text] [PDF]