Maintaining genomic integrity in mammalian early embryos, which are deficient in DNA damage repair, is critical for normal preimplantation and subsequent development. Abnormalities in DNA damage repair in preimplantation embryos can cause not only developmental arrest, but also diseases such as congenital disorders and cancers. Histone H4 lysine 20 monomethylation (H4K20me1) is involved in DNA damage repair and regulation of gene expression. However, little is known about the role of H4K20me1 during mouse preimplantation development. In this study, we revealed that H4K20me1 mediated by SETD8 is involved in maintaining genomic integrity. H4K20me1 was present throughout preimplantation development. In addition, reduction in the level of H4K20me1 by inhibition of SETD8 activity or a dominant-negative mutant of histone H4 resulted in developmental arrest at the S/G2 phase and excessive accumulation of DNA double-strand breaks. Together, our results suggest that H4K20me1, a type of epigenetic modification, is associated with the maintenance of genomic integrity and is essential for preimplantation development. A better understanding of the mechanisms involved in maintaining genome integrity during preimplantation development could contribute to advances in reproductive medicine and technology.

中文翻译：

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H4K20 单甲基化抑制导致小鼠植入前胚胎中基因组完整性的丧失

在缺乏 DNA 损伤修复的哺乳动物早期胚胎中保持基因组完整性对于正常的植入前和后续发育至关重要。植入前胚胎中 DNA 损伤修复的异常不仅会导致发育停滞，还会导致先天性疾病和癌症等疾病。组蛋白 H4 赖氨酸 20 单甲基化 (H4K20me1) 参与 DNA 损伤修复和基因表达调控。然而，关于 H4K20me1 在小鼠植入前发育过程中的作用知之甚少。在这项研究中，我们揭示了由 SETD8 介导的 H4K20me1 参与维持基因组完整性。H4K20me1 在整个植入前发育过程中都存在。此外，通过抑制 SETD8 活性或组蛋白 H4 的显性负突变体来降低 H4K20me1 水平，导致发育停滞在 S/G2 期和 DNA 双链断裂的过度积累。总之，我们的结果表明 H4K20me1 是一种表观遗传修饰，与维持基因组完整性有关，并且对于植入前发育至关重要。更好地了解在胚胎植入前发育过程中维持基因组完整性的机制可能有助于生殖医学和技术的进步。