Epigenetic modifications undergo drastic erasure and reestablishment after fertilization. This reprogramming is required for proper embryonic development and cell differentiation. In mammals, some histone modifications are not completely reprogrammed and play critical roles in later development. In contrast, in nonmammalian vertebrates, most histone modifications are thought to be more intensively erased and reestablished by the stage of zygotic genome activation (ZGA). However, histone modifications that escape reprogramming in nonmammalian vertebrates and their potential functional roles remain unknown. Here, we quantitatively and comprehensively analyzed histone modification dynamics during epigenetic reprogramming in Japanese killifish, medaka (Oryzias latipes) embryos. Our data revealed that H3K27ac, H3K27me3, and H3K9me3 escape complete reprogramming, whereas H3K4 methylation is completely erased during cleavage stage. Furthermore, we experimentally showed the functional roles of such retained modifications at early stages: (i) H3K27ac premarks promoters during the cleavage stage, and inhibition of histone acetyltransferases disrupts proper patterning of H3K4 and H3K27 methylation at CpG-dense promoters, but does not affect chromatin accessibility after ZGA; (ii) H3K9me3 is globally erased but specifically retained at telomeric regions, which is required for maintenance of genomic stability during the cleavage stage. These results expand the understanding of diversity and conservation of reprogramming in vertebrates, and unveil previously uncharacterized functions of histone modifications retained during epigenetic reprogramming.

中文翻译：

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青鳉早期发育中表观遗传重编程过程中组蛋白标记的不完全擦除

表观遗传修饰在受精后经历彻底的消除和重建。这种重编程是适当的胚胎发育和细胞分化所必需的。在哺乳动物中，一些组蛋白修饰并未完全重新编程，并在以后的发育中发挥关键作用。相比之下，在非哺乳动物脊椎动物中，大多数组蛋白修饰被认为在合子基因组激活（ZGA）阶段被更强烈地擦除和重建。然而，在非哺乳动物脊椎动物中逃避重编程的组蛋白修饰及其潜在的功能作用仍然未知。在这里，我们定量、全面地分析了日本青鳉鱼（Oryzias latipes）胚胎表观遗传重编程过程中的组蛋白修饰动态。我们的数据显示，H3K27ac、H3K27me3 和 H3K9me3 逃脱了完全重编程，而 H3K4 甲基化在裂解阶段被完全擦除。此外，我们通过实验证明了此类保留修饰在早期阶段的功能作用：（i）H3K27ac 在裂解阶段预先标记启动子，组蛋白乙酰转移酶的抑制会破坏 CpG 密集启动子处 H3K4 和 H3K27 甲基化的正确模式，但不影响ZGA 后染色质可及性；(ii) H3K9me3 被整体擦除，但在端粒区域被特异性保留，这是在裂解阶段维持基因组稳定性所必需的。这些结果扩展了对脊椎动物重编程多样性和保守性的理解，并揭示了表观遗传重编程过程中保留的组蛋白修饰的先前未表征的功能。