Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom.
PLoS One. 2007 Sep 12;2(9):e860. doi: 10.1371/journal.pone.0000860.
The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.
PRINCIPAL FINDINGS/METHODOLOGY: We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.
CONCLUSIONS/SIGNIFICANCE: We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome.
雌性体细胞谱系中无活性的 X 染色体在雌性生殖细胞谱系的发育过程中被重新激活。在小鼠中，对位于 X 染色体上的 X 连锁基因的蛋白质产物和/或转基因的分析表明，重激活发生在原始生殖细胞到达生殖嵴之后。
主要发现/方法：我们提供的证据表明，无活性 X 染色体的表观遗传重编程比以前认为的更早开始，大约在原始生殖细胞（PGC）穿过后肠的时候。具体来说，我们发现 Xist RNA 的表达，即建立染色体沉默的主要信号，在迁移的 PGC 中被熄灭。这伴随着 Polycomb 组抑制蛋白 Eed 和 Suz(12)的位移，以及无活性 X 相关组蛋白修饰，即组蛋白 H3 赖氨酸 27 的甲基化的丢失。
结论/意义：我们得出结论，原始生殖细胞中的 X 重激活是渐进发生的，由 Xist RNA 在生殖细胞迁移到生殖嵴的过程中熄灭引发。我们观察到的事件让人联想到小鼠植入前胚胎内细胞团中父本 X 染色体的 X 重激活，并提出了一个统一的模型，即多能性程序的执行抑制了 Xist RNA，从而触发了 X 染色体表观遗传沉默的逐步逆转。
