Methylation dynamics of imprinted genes in mouse germ cells
- PMID: 11944985
- DOI: 10.1006/geno.2002.6732
Methylation dynamics of imprinted genes in mouse germ cells
Abstract
DNA methylation differences between maternal and paternal alleles of many imprinted genes are inherited from the male and female gametes and subsequently maintained during development. However, the stages of gametogenesis during which methylation imprints are established have not been well defined. In this study, we used bisulfite sequencing to determine the methylation dynamics of the imprinted genes small nuclear ribonucleoprotein N (Snrpn), insulin-like growth factor 2 receptor (Igf2r), mesoderm-specific transcript (Mest; formerly Peg1), paternally expressed gene 3 (Peg3), and H19 fetal liver mRNA (H19). We identified regions in the maternally imprinted genes (Snrpn, Mest, and Peg3) that were unmethylated in sperm but 100% methylated in mature oocytes. Igf2r, which is expressed from the maternal allele, was completely methylated within intronic differentially methylated region 2 in oocytes and unmethylated in sperm. The 5' region of H19, a paternally imprinted gene, was completely methylated in sperm and unmethylated in oocytes. We examined the methylation status of Snrpn during oocyte growth and maturation. Whereas the DNA of non-growing oocytes was mostly unmethylated, mid-size growing oocytes had a mosaic pattern of allelic methylation, and full acquisition of the methylation imprint was complete by metaphase II. We have identified regions within imprinted genes that show gamete-specific methylation patterns in mature germ cells and demonstrated that maternal methylation imprints on at least one imprinted gene, Snrpn, are established during the postnatal growth phase of oogenesis. Thus, whereas paternal imprints seem to be established early (in diploid gonocytes well before the onset of meiosis), maternal imprints are established late (in growing oocytes that are arrested in the diplotene stage of meiosis). These findings raise the possibility that assisted reproductive technologies that involve in vitro maturation of oocytes may result in developmental abnormalities due to incomplete methylation imprints in immature oocytes.
Similar articles
-
Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos.Hum Mol Genet. 2003 Nov 15;12(22):2873-9. doi: 10.1093/hmg/ddg315. Epub 2003 Sep 18. Hum Mol Genet. 2003. PMID: 14500540
-
Oocyte growth-dependent progression of maternal imprinting in mice.Genes Cells. 2006 Apr;11(4):353-61. doi: 10.1111/j.1365-2443.2006.00943.x. Genes Cells. 2006. PMID: 16611239
-
Diploid parthenogenetic embryos adopt a maternal-type methylation pattern on both sets of maternal chromosomes.Genomics. 2008 Feb;91(2):121-8. doi: 10.1016/j.ygeno.2007.10.005. Epub 2007 Nov 26. Genomics. 2008. PMID: 18036775
-
Origins of extreme sexual dimorphism in genomic imprinting.Cytogenet Genome Res. 2006;113(1-4):36-40. doi: 10.1159/000090813. Cytogenet Genome Res. 2006. PMID: 16575161 Review.
-
Imprinting in the germ line.Stem Cells. 2001;19(4):287-94. doi: 10.1634/stemcells.19-4-287. Stem Cells. 2001. PMID: 11463948 Review.
Cited by
-
Environmental Impact on Male (In)Fertility via Epigenetic Route.J Clin Med. 2020 Aug 5;9(8):2520. doi: 10.3390/jcm9082520. J Clin Med. 2020. PMID: 32764255 Free PMC article. Review.
-
Acrylamide toxic effects on mouse oocyte quality and fertility in vivo.Sci Rep. 2015 Jun 25;5:11562. doi: 10.1038/srep11562. Sci Rep. 2015. PMID: 26108138 Free PMC article.
-
Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development.Dev Cell. 2013 Feb 11;24(3):310-23. doi: 10.1016/j.devcel.2012.12.015. Epub 2013 Jan 24. Dev Cell. 2013. PMID: 23352810 Free PMC article.
-
A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation.PLoS Genet. 2007 Feb 9;3(2):e20. doi: 10.1371/journal.pgen.0030020. Epub 2006 Dec 18. PLoS Genet. 2007. PMID: 17291163 Free PMC article.
-
H19 imprinting control region methylation requires an imprinted environment only in the male germ line.Mol Cell Biol. 2010 Mar;30(5):1108-15. doi: 10.1128/MCB.00575-09. Epub 2009 Dec 28. Mol Cell Biol. 2010. PMID: 20038532 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous