Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells
Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells
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DOI：
10.1371/journal.pone.0000860
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发表时间：
2007-09-12
期刊：
影响因子：
3.7
通讯作者：
Brockdorff, Neil
中科院分区：
文献类型：
--
作者：
de Napoles, Mariana;Nesterova, Tatyana;Brockdorff, Neil
背景资料。在雌性生殖细胞谱系的发育过程中，雌性体细胞谱系的非活性X染色体特征被重新激活。在小鼠中，X连锁基因和/或位于X染色体上的转基因的蛋白质产物分析表明，在原始生殖细胞到达生殖器脊后发生重新激活。主要发现/方法。我们提出的证据表明，不活跃的X染色体的表观遗传学重新编程比之前认为的更早开始，大约在原始生殖细胞(PGC)通过后肠迁移的时候。具体地说，我们发现Xist RNA表达，建立染色体沉默的主要信号，在迁移的PGCs中被熄灭。伴随而来的是多梳基抑制蛋白Eed和Suz(12)的置换，以及失活的X相关的组蛋白修饰，组蛋白H3赖氨酸27的甲基化。结论/意义。我们得出结论，原始生殖细胞中的X重新激活是逐步发生的，由Xist RNA的消亡开始，大约在生殖细胞通过后肠迁移到生殖器脊的时候。我们观察到的这些事件让人想起了小鼠植入前胚胎内细胞团细胞中父系X染色体的重新激活，并提出了一个统一的模型，在该模型中，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渐进逆转。
Background. 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.