title: Ontogeny, conservation and functional significance of maternally inherited DNA methylation at two classes of non-imprinted genes.
abstract: A functional role for DNA methylation has been well-established at imprinted loci, which inherit methylation uniparentally, most commonly from the mother via the oocyte. Many CpG islands not associated with imprinting also inherit methylation from the oocyte, although the functional significance of this, and the common features of the genes affected, are unclear. We identify two major subclasses of genes associated with these gametic differentially methylated regions (gDMRs), namely those important for brain and for testis function. The gDMRs at these genes retain the methylation acquired in the oocyte through preimplantation development, but become fully methylated postimplantation by de novo methylation of the paternal allele. Each gene class displays unique features, with the gDMR located at the promoter of the testis genes but intragenically for the brain genes. Significantly, demethylation using knockout, knockdown or pharmacological approaches in mouse stem cells and fibroblasts resulted in transcriptional derepression of the testis genes, indicating that they may be affected by environmental exposures, in either mother or offspring, that cause demethylation. Features of the brain gene group suggest that they might represent a pool from which many imprinted genes have evolved. The locations of the gDMRs, as well as methylation levels and repression effects, were also conserved in human cells.
authors: Centre for Molecular Biosciences, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK.
authors: Charlotte E
authors: CE
authors: Rutledge
authors: Avinash
authors: A
authors: Thakur
authors: Karla M
authors: KM
authors: O'Neill
authors: Rachelle E
authors: RE
authors: Irwin
authors: Shun
authors: S
authors: Sato
authors: Ken
authors: K
authors: Hata
authors: Colum P
authors: CP
authors: Walsh
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009865:Oocytes / Q000378:metabolism; D013737:Testis / Q000378:metabolism
chemical_list: C498796:Dnmt3l protein, mouse; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: DNA methylation; Epigenetics; Imprinting