Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice
Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice
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DOI：
10.1242/dev.005611
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发表时间：
2007-07-15
期刊：
影响因子：
4.6
通讯作者：
Saitou, Mitinori
中科院分区：
文献类型：
--
作者：
Seki, Yoshiyuki;Yamaji, Masashi;Saitou, Mitinori
我们之前报道过，小鼠的原始生殖细胞（PGC）在迁移过程中消除了全基因组DNA甲基化和组蛋白H3赖氨酸9二甲基化（H3K9me2），取而代之的是获得高水平的H3K27三甲基化（H3K27me3），这一过程对于生殖系潜在全能性的重建可能至关重要。我们在这里探索了与这种表观遗传重编程相关的细胞动力学。我们发现 PGC 以逐个细胞的方式逐渐消除 H3K9me2 和上调 H3K27me3，这可能取决于它们的发育成熟度。在 H3K9 去甲基化开始之前或同时，PGC 进入细胞周期的 G2 停滞，该停滞显然持续到它们获得高 H3K27me3 水平。有趣的是，PGCs表现出对RNA聚合酶II依赖性转录的抑制，这种抑制在G2期H3K9me2开始减少后开始，并在获得高水平H3K27me3后逐渐减弱。表观遗传重编程和转录静止与 Nanos3 的功能无关。我们发现，在 H3K9 去甲基化之前，PGC 专门抑制必需的组蛋白甲基转移酶 GLP，而不特异性上调组蛋白去甲基化酶。我们认为，一种必需酶的主动抑制和随后独特的细胞动力学可能确保在迁移的 PGC 中成功实施全基因组表观遗传重编程。
We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 dimethylation (H3K9me2), and instead acquire high levels of tri-methylation of H3K27 (H3K27me3) during their migration, a process that might be crucial for the re- establishment of potential totipotency in the germline. We here explored a cellular dynamics associated with this epigenetic reprogramming. We found that PGCs undergo erasure of H3K9me2 and upregulation of H3K27me3 in a progressive, cell-by-cell manner, presumably depending on their developmental maturation. Before or concomitant with the onset of H3K9 demethylation, PGCs entered the G2 arrest of the cell cycle, which apparently persisted until they acquired high H3K27me3 levels. Interestingly, PGCs exhibited repression of RNA polymerase II-dependent transcription, which began after the onset of H3K9me2 reduction in the G2 phase and tapered off after the acquisition of high-level H3K27me3. The epigenetic reprogramming and transcriptional quiescence were independent from the function of Nanos3. We found that before H3K9 demethylation, PGCs exclusively repress an essential histone methyltransferase, GLP, without specifically upregulating histone demethylases. We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs.