title: DNA methyltransferase 1 (Dnmt1) mutation affects Snrpn imprinting in the mouse male germ line.
abstract: DNA methylation and DNA methyltransferases are essential for spermatogenesis. Mutations in the DNA methyltransferase Dnmt1 gene exert a paternal effect on epigenetic states and phenotypes of offspring, suggesting that DNMT1 is important for the epigenetic remodeling of the genome that takes place during spermatogenesis. However, the specific role of DNMT1 in spermatogenesis and the establishment of genomic imprints in the male germ line remains elusive. To further characterize the effect of DNMT1 deficiency on the resetting of methylation imprints during spermatogenesis, we analyzed the methylation profiles of imprinted regions in the spermatozoa of mice that were heterozygous for a Dnmt1 loss-of-function mutation. The mutation did not affect the H19 or IG differentially methylated regions (DMRs) that are usually highly methylated but led to a partial hypermethylation of the Snrpn DMR, a region that should normally be unmethylated in mature spermatozoa. This defect does not appear in mouse models with mutations in Dnmt3a and Mthfr genes and, therefore, it is specific for the Dnmt1 gene and is suggestive of a role of DNMT1 in imprint resetting or maintenance in the male germ line.
authors.affiliation: Department of Human Genetics, McGill University, Montréal, QC H3A 1B1, Canada.
authors.forename: Aabida
authors.initials: A
authors.lastname: Saferali
authors.forename: Sanny
authors.initials: S
authors.lastname: Moussette
authors.forename: Donovan
authors.initials: D
authors.lastname: Chan
authors.forename: Jacquetta
authors.initials: J
authors.lastname: Trasler
authors.forename: Taiping
authors.initials: T
authors.lastname: Chen
authors.forename: Rima
authors.initials: R
authors.lastname: Rozen
authors.forename: Anna K
authors.initials: AK
authors.lastname: Naumova
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D017353:Gene Deletion; D018392:Genomic Imprinting / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism
chemical_list: C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D009687:Nuclear Proteins; C486713:SNURF protein, mouse; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619381:Dnmt1 protein, mouse