title: Imprinting analysis of the mouse chromosome 7C region in DNMT1-null embryos.
abstract: The mouse chromosome 7C, orthologous to the human 15q11-q13 has an imprinted domain, where most of the genes are expressed only from the paternal allele. The imprinted domain contains paternally expressed genes, Snurf/Snrpn, Ndn, Magel2, Mkrn3, and Frat3, C/D-box small nucleolar RNAs (snoRNAs), and the maternally expressed gene, Ube3a. Imprinted expression in this large (approximately 3-4 Mb) domain is coordinated by a bipartite cis-acting imprinting center (IC), located upstream of the Snurf/Snrpn gene. The molecular mechanism how IC regulates gene expression of the whole domain remains partially understood. Here we analyzed the relationship between imprinted gene expression and DNA methylation in the mouse chromosome 7C using DNA methyltransferase 1 (DNMT1)-null mutant embryos carrying Dnmt1(ps) alleles, which show global loss of DNA methylation and embryonic lethality. In the DNMT1-null embryos at embryonic day 9.5, the paternally expressed genes were biallelically expressed. Bisulfite DNA methylation analysis revealed loss of methylation on the maternal allele in the promoter regions of the genes. These results demonstrate that DNMT1 is necessary for monoallelic expression of the imprinted genes in the chromosome 7C domain, suggesting that DNA methylation in the secondary differentially methylated regions (DMRs), which are acquired during development serves primarily to control the imprinted expression from the maternal allele in the mouse chromosome 7C.
authors.affiliation: Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nakagaki
authors.affiliation: Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.
authors.forename: Hanae
authors.initials: H
authors.lastname: Osanai
authors.affiliation: Division of Functional Genomics, Center for Frontier Life Sciences, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan. Electronic address: kishino@nagasaki-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kishino
mesh_terms: D000818:Animals; D001483:Base Sequence; D002875:Chromosomes; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018392:Genomic Imprinting; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse
keywords: Dnmt1; Frat3; Genomic imprinting; Magel 2; Mkrn 3; Ndn; Snrpn; Ube3a; snoRNA