The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development
The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development
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DOI：
10.1093/hmg/9.19.2885
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发表时间：
2000-11-22
影响因子：
3.5
通讯作者：
Bartolomei, MS
中科院分区：
文献类型：
--
作者：
Davis, TL;Yang, GJ;Bartolomei, MS
DNA甲基化的差异区分了许多印记基因的母本和父本等位基因，从配子遗传并在整个发育过程中维持的等位基因特异性甲基化已被提议作为候选印记标记。为了确定甲基化是如何在种系中建立的，我们分析了小鼠胚胎配子发生过程中母本表达、父本甲基化的 H19 基因的等位基因甲基化模式。我们在此表明，雄性和雌性妊娠中期胚胎生殖细胞中的两个亲本等位基因均缺乏甲基化，这表明在此之前生殖细胞中的甲基化印记已被消除。此外，我们证明，雄性种系中父本和母本等位基因的高甲基化发生在不同的时间，尽管父本等位基因在胎儿阶段变得高甲基化，但母本等位基因的甲基化在围产期开始；并在出生后持续到减数分裂开始，？在配子发生过程中亲本 H19 等位基因甲基化的差异获得意味着两个未甲基化等位基因仍然可以彼此区分。因此，在缺乏 DNA 甲基化的情况下，其他表观遗传机制似乎在雄性生殖细胞发育过程中维持 H19 基因座的亲本身份。
Differences in DNA methylation distinguish the maternal and paternal alleles of many imprinted genes, Allele specific methylation that is inherited from the gametes and maintained throughout development has been proposed as a candidate imprinting mark. To determine how methylation is established in the germline, we have analyzed the allelic methylation patterns of the maternally expressed, paternally methylated H19 gene during gametogenesis in the mouse embryo. We show here that both parental alleles are devoid of methylation in male and female mid-gestation embryonic germ cells, suggesting that methylation imprints are erased in the germ cells prior to this time. In addition, we demonstrate that the subsequent hypermethylation of the paternal and maternal alleles in the male germline occurs at different times, Although the paternal allele becomes hypermethylated during fetal stages, methylation of the maternal allele begins during perinatal stages;and continues postnatally through the onset of meiosis, The? differential acquisition of methylation on the parental H19 alleles during gametogenesis implies that the two unmethylated alleles can still be distinguished from each other, Thus, in the absence of DNA methylation, other epigenetic mechanism(s) appear to maintain parental identity at the H19 locus during male germ cell development.