Department of Human Genetics, McGill University, Montréal, QC H3A 1B1, Canada.
Genome. 2012 Sep;55(9):673-82. doi: 10.1139/g2012-056. Epub 2012 Sep 11.
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.
DNA 甲基化和 DNA 甲基转移酶对于精子发生至关重要。DNA 甲基转移酶 Dnmt1 基因的突变对后代的表观遗传状态和表型产生父系效应，表明 DNMT1 对于精子发生过程中基因组的表观遗传重塑很重要。然而，DNMT1 在精子发生和雄性生殖系中基因组印记建立中的具体作用仍难以捉摸。为了进一步描述 DNMT1 缺乏对精子发生过程中甲基化印记重新设定的影响，我们分析了 Dnmt1 功能丧失突变杂合子小鼠精子中印记区域的甲基化谱。该突变不影响通常高度甲基化的 H19 或 IG 差异甲基化区域 (DMR)，但导致 Snrpn DMR 部分过度甲基化，该区域在成熟精子中通常应是非甲基化的。这种缺陷不会出现在 Dnmt3a 和 Mthfr 基因突变的小鼠模型中，因此它是特定于 Dnmt1 基因的，并提示 DNMT1 在雄性生殖系中的印记重置或维持中发挥作用。
