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Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis.

机译:H19甲基化印记的获得在精子发生过程中在亲本等位基因上不同地发生。

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摘要

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. Copyright 1999 Academic Press.
机译:印迹的小鼠H19基因在表达的母本等位基因上被甲基化,而在沉默的父本等位基因上被甲基化。相对于H19转录起始位点,位于-2到-4 kb之间的2 kb差异甲基化区域已被提议作为印记标记,因为该区域中的高甲基化是从精子继承并在整个发育过程中保留在父本等位基因上。在这里,我们描述了产后男性生殖细胞发育过程中H19位点甲基化模式的时间分析。在整个精子发生过程中,在父本等位基因上的2 KB区域被甲基化,这表明该甲基化是在出生后雄性小鼠恢复有丝分裂之前在该区域获得的。同样,在恢复有丝分裂之前,一半以上的母亲等位基因是高甲基化的。但是,剩余的母体等位基因在减数分裂I完成之前不会甲基化,这表明该区域的从头甲基化是一个连续的过程。在二倍体,有丝分裂的精原细胞中,在精子中和在父本等位基因上甲基化的H19启动子近端序列被甲基化。母本等位基因在减数分裂前期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差异地获得甲基化。版权所有1999 Academic Press。

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