Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis
Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis
复制标题
DOI：
10.1093/hmg/9.14.2183
复制
发表时间：
2000-09-01
影响因子：
3.5
通讯作者：
Jeanpierre, M
中科院分区：
文献类型：
--
作者：
Kerjean, A;Dupont, JM;Jeanpierre, M
在生殖细胞成熟过程中，亲本特异性表观遗传修饰在哺乳动物基因组的一部分基因上留下了印记，然而，它们建立的确切时间仍有待确定。CpG二核苷酸的甲基化已被证明是亲本印记的一部分，我们研究了在人类精子发生过程中，生殖细胞中父本等位基因的甲基化模式特征是如何建立的。研究了两个具有代表性的印迹基因H19和MEST/PEG1。实验采用亚硫酸盐测序法对男性生殖细胞分化不同阶段的微解剖单个细胞进行测序。我们发现，这两个基因在胎儿精原细胞中都未甲基化，这表明所有先前存在的甲基化印记都已经在这一阶段被抹去。MEST/PEG1基因在随后的所有青春期后精子发生阶段（包括成熟精子）都保持未甲基化。我们的研究结果表明，遗传自父母的甲基化印记首先在胎儿早期在雄性生殖系中被消除。只有在成年睾丸的精原分化过程中，父系特异性印记才会重新建立。
Parental-specific epigenetic modifications are imprinted on a subset of genes in the mammalian genome during germ cell maturation, However, the precise timing of their establishment remains to be determined. Methylation of CpG dinucleotides has been shown to be a part of the parental imprint, We have examined how the methylation pattern characteristic of the paternal allele in germ cells are established during human spermatogenesis. Two representative imprinted genes, H19 and MEST/PEG1, were studied. The experiments were performed using the bisulphite sequencing method on microdissected individual cells at different stages of male germ cell differentiation. We show that both genes are unmethylated in fetal spermatogonia, suggesting that all pre-existing methylation imprints are already erased by this stage, The MEST/PEG1 gene remains unmethylated at all subsequent post-pubertal stages of spermatogenesis, including mature spermatozoa, The methylation of H19 typical of the paternal allele first appears in a subset of adult spermatogonia and then is maintained in spermatocytes, spermatids and mature spermatozoa, Our results suggest that the methylation imprint inherited from the parents is first erased in the male germ line at an early fetal stage. The paternal-specific imprint is re-established only later, during spermatogonial differentiation in the adult testis.