Department of Molecular and Cellular Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California, United States of America.
PLoS One. 2011;6(8):e23848. doi: 10.1371/journal.pone.0023848. Epub 2011 Aug 19.
Mammalian germ cells undergo global reprogramming of DNA methylation during their development. Global DNA demethylation occurs around the time when the primordial germ cells colonize the embryonic gonads and this coincides with dynamic changes in chromatin composition. Global de novo DNA methylation takes place with remarkably different dynamics between the two sexes, prospermatogonia attaining methylation during fetal stages and oocytes attaining methylation postnatally. Our hypothesis was that dynamic changes in chromatin composition may precede or accompany the wave of global DNA de novo methylation as well. We used immunocytochemistry to measure global DNA methylation and chromatin components in male and female mouse fetal germ cells compared to control somatic cells of the gonad. We found that global DNA methylation levels sharply increased in male germ cells at 17.5 days post coitum, but remained low in female germ cells at all fetal stages. Global changes in chromatin composition: i, preceded global DNA methylation in fetal germ cells; ii, sex specifically occurred in male but not in female germ cells; iii, affected active and repressive histone marks and iv, included histone tail and histone globular domain modifications. Our data suggest that dynamic changes of chromatin composition may provide a framework for the pattern of male-specific de novo DNA methylation in prospermatogonia.
哺乳动物生殖细胞在发育过程中经历 DNA 甲基化的全局重编程。原生殖细胞定植于胚胎性腺时，会发生全基因组 DNA 去甲基化，这与染色质组成的动态变化相吻合。在雌雄两性中，新生成的全基因组 DNA 甲基化以显著不同的动力学发生，雄性的精原细胞在胎儿期获得甲基化，而雌性的卵母细胞在出生后获得甲基化。我们假设染色质组成的动态变化可能先于或伴随着新生成的全基因组 DNA 甲基化波发生。我们使用免疫细胞化学技术，测量了与性腺中的对照体细胞核相比，雄性和雌性小鼠胎儿生殖细胞中的全基因组 DNA 甲基化和染色质成分。我们发现，在雄性生殖细胞中，全基因组 DNA 甲基化水平在妊娠 17.5 天时急剧增加，但在所有胎儿阶段的雌性生殖细胞中仍保持较低水平。染色质组成的全局变化：i）在胎儿生殖细胞中先于全基因组 DNA 甲基化发生；ii）特异性地发生在雄性生殖细胞中，而不在雌性生殖细胞中；iii）影响活性和抑制性组蛋白标记；iv）包括组蛋白尾部和组蛋白球状结构域修饰。我们的数据表明，染色质组成的动态变化可能为精原细胞中雄性特异性新生成的 DNA 甲基化模式提供了一个框架。
