Forming an embryo from a zygote poses an apparent conflict for epigenetic regulation. On the one hand, the de novo induction of cell fate identities requires the establishment and subsequent maintenance of epigenetic information to harness developmental gene expression. On the other hand, the embryo depends on cell proliferation, and every round of DNA replication dilutes preexisting histone modifications by incorporation of new unmodified histones into chromatin. Here, we investigated the possible relationship between the propagation of epigenetic information and the developmental cell proliferation during Xenopus embryogenesis. We systemically inhibited cell proliferation during the G1/S transition in gastrula embryos and followed their development until the tadpole stage. Comparing wild-type and cell cycle-arrested embryos, we show that the inhibition of cell proliferation is principally compatible with embryo survival and cellular differentiation. In parallel, we quantified by mass spectrometry the abundance of a large set of histone modification states, which reflects the developmental maturation of the embryonic epigenome. The arrested embryos developed abnormal stage-specific histone modification profiles (HMPs), in which transcriptionally repressive histone marks were overrepresented. Embryos released from the cell cycle block during neurulation reverted toward normality on morphological, molecular, and epigenetic levels. These results suggest that the cell cycle block by HUA alters stage-specific HMPs. We propose that this influence is strong enough to control developmental decisions, specifically in cell populations that switch between resting and proliferating states such as stem cells.

中文翻译：

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系统性细胞周期阻断会影响非洲爪蟾胚胎发生过程中阶段特异性组蛋白修饰谱。

从受精卵形成胚胎对表观遗传调控造成了明显的冲突。一方面，细胞命运身份的从头诱导需要表观遗传信息的建立和随后的维护，以利用发育基因表达。另一方面，胚胎依赖于细胞增殖，每轮 DNA 复制都会通过将新的未修饰组蛋白掺入染色质来稀释先前存在的组蛋白修饰。在这里，我们研究了爪蟾胚胎发生过程中表观遗传信息的传播与发育细胞增殖之间的可能关系。我们系统地抑制了原肠胚 G1/S 期细胞增殖，并跟踪其发育直至蝌蚪阶段。比较野生型和细胞周期停滞的胚胎，我们发现细胞增殖的抑制基本上与胚胎存活和细胞分化相容。与此同时，我们通过质谱法量化了大量组蛋白修饰状态的丰度，这反映了胚胎表观基因组的发育成熟程度。停滞的胚胎发育出异常的阶段特异性组蛋白修饰谱（HMP），其中转录抑制组蛋白标记被过度表达。在神经形成过程中从细胞周期阻滞中释放的胚胎在形态、分子和表观遗传水平上恢复正常。这些结果表明 HUA 阻断细胞周期会改​​变阶段特异性 HMP。我们认为这种影响足以控制发育决策，特别是在静息状态和增殖状态之间切换的细胞群（例如干细胞）中。