Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis
Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis
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DOI：
10.1006/geno.1999.5813
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发表时间：
1999-05-15
期刊：
影响因子：
4.4
通讯作者：
Bartolomei, MS
中科院分区：
文献类型：
--
作者：
Davis, TL;Trasler, JM;Bartolomei, MS
印记小鼠 H19 基因在表达的母本等位基因上低甲基化，在沉默父本等位基因上高甲基化。相对于 H19 转录起始位点，位于 -2 至 -4 kb 的 2 kb 差异甲基化区域被提议充当印记标记，因为该区域的高甲基化是从精子遗传的，并在整个发育过程中保留在父本等位基因上。在这里，我们描述了出生后雄性生殖细胞发育过程中 H19 位点甲基化模式的时间分析。 2-kb 区域在整个精子发生过程中在父本等位基因上被甲基化，这表明在产后雄性小鼠有丝分裂恢复之前该区域获得了甲基化。同样，超过一半的母体等位基因在有丝分裂恢复之前被高甲基化。然而，剩余的母体等位基因直到减数分裂 I 完成才高度甲基化，表明该区域的从头甲基化是一个连续的过程。靠近 H19 启动子的序列在精子中和体细胞中的父本等位基因上甲基化，在二倍体有丝分裂精原细胞中差异甲基化。在减数分裂前期，母体等位基因在该区域变得高度甲基化。因此，亲本 H19 等位基因在雄性种系中获得差异性甲基化。 (C) 1999 年学术出版社。
The imprinted mouse H19 gene is hypomethylated on the expressed maternal allele and hypermethylated on the silent paternal allele. A 2-kb region of differential methylation located from -2 to -4 kb relative to the H19 transcriptional start site has been proposed to act as the imprinting mark since hypermethylation in this region is inherited from sperm and retained on the paternal allele throughout development. Here, we describe a temporal analysis of the methylation patterns at the H19 locus during postnatal male germ cell development. The 2-kb region is methylated on the paternal allele throughout spermatogenesis, suggesting that methylation is acquired in this region prior to the resumption of mitosis in postnatal male mice. Likewise, more than half of the maternal alleles are hypermethylated prior to the resumption of mitosis. However, the remaining maternal alleles are not hypermethylated until the completion of meiosis I, indicating that de novo methylation in this region is a continuous process. Sequences proximal to the H19 promoter, which are methylated in spermatozoa and on the paternal allele in somatic cells, are differentially methylated in diploid, mitotic spermatogonia. The maternal allele becomes hypermethylated in this region during meiotic prophase. Thus, the parental H19 alleles acquire methylation differentially in the male germline. (C) 1999 Academic Press.