Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
PLoS Biol. 2021 Sep 7;19(9):e3001377. doi: 10.1371/journal.pbio.3001377. eCollection 2021 Sep.
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.
从受精卵中形成胚胎对表观遗传调控构成了明显的冲突。一方面，新诱导的细胞命运特征需要建立和随后维持表观遗传信息，以利用发育基因表达。另一方面，胚胎依赖于细胞增殖，并且每一轮 DNA 复制都会通过将新的未修饰组蛋白掺入染色质中来稀释先前存在的组蛋白修饰。在这里，我们研究了在非洲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。我们在原肠胚期通过系统抑制 G1/S 期的细胞增殖，然后观察它们的发育直至蝌蚪阶段。将野生型和细胞周期阻滞的胚胎进行比较，我们表明，细胞增殖的抑制主要与胚胎存活和细胞分化兼容。同时，我们通过质谱法定量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。被阻滞的胚胎发育出异常的阶段特异性组蛋白修饰图谱（HMPs），其中转录抑制性组蛋白标记物过度表达。在神经胚形成期间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 引起的细胞周期阻滞改变了阶段特异性 HMPs。我们提出，这种影响足以控制发育决策，特别是在像干细胞这样在静止和增殖状态之间切换的细胞群体中。
