Lucifero Diana, Mann Mellissa R W, Bartolomei Marisa S, Trasler Jacquetta M
McGill University, Montreal Children's Hospital Research Institute and Departments of Pediatrics, Human Genetics and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3H 1P3.
Hum Mol Genet. 2004 Apr 15;13(8):839-49. doi: 10.1093/hmg/ddh104. Epub 2004 Mar 3.
Imprinted genes are differentially marked during germ cell development to allow for their eventual parent-of-origin specific expression. A subset of imprinted genes becomes methylated during oocyte growth in both mouse and human. However the timing and mechanisms of methylation acquisition are unknown. Here, we examined the methylation of the Snrpn, Igf2r, Peg1 and Peg3 differentially methylated regions in postnatal growing mouse oocytes. Our findings indicate that methylation was acquired asynchronously at these different genes. Further analysis of Snrpn DMR1 revealed that parental alleles retain an epigenetic memory of their origin as the two alleles were recognized in a parental-specific manner in the absence of DNA methylation. In addition, we show that methylation acquisition was probably related to oocyte diameter and coincided with the accumulation of Dnmt3a, Dnmt3b and Dnmt3L transcripts. Methylation of the repetitive retroviral-like intracisternal A particle also occurred during this same window of oocyte growth. These findings contribute to our understanding of the epigenetic mechanisms underlying imprint acquisition during female germ cell development and have implications for the practice of assisted reproductive technologies.
印记基因在生殖细胞发育过程中被差异性标记，以使其最终实现源自亲本的特异性表达。在小鼠和人类中，一部分印记基因在卵母细胞生长过程中会发生甲基化。然而，甲基化获得的时间和机制尚不清楚。在此，我们检测了出生后生长中的小鼠卵母细胞中Snrpn、Igf2r、Peg1和Peg3差异甲基化区域的甲基化情况。我们的研究结果表明，这些不同基因的甲基化是异步获得的。对Snrpn DMR1的进一步分析显示，亲本等位基因保留了其起源的表观遗传记忆，因为在没有DNA甲基化的情况下，这两个等位基因以亲本特异性的方式被识别。此外，我们表明甲基化的获得可能与卵母细胞直径有关，并且与Dnmt3a、Dnmt3b和Dnmt3L转录本的积累同时发生。重复性逆转录病毒样的内源性A颗粒的甲基化也发生在卵母细胞生长的同一时期。这些发现有助于我们理解雌性生殖细胞发育过程中印记获得的表观遗传机制，并对辅助生殖技术的实践具有启示意义。
