Genome stability is critical for the normal development of preimplantation embryos, as DNA damages may result in mutation and even embryo lethality. Anti-silencing factor 1A (ASF1A) is a histone chaperone and enriched in the MII oocytes as a maternal factor, which may be associated with the maintenance of genome stability. Thus, this study was undertaken to explore the role of ASF1A in maintaining the genome stability of early mouse embryos. The ASF1A expressed in the preimplantation embryos and displayed a dynamic pattern throughout the early embryonic development. Inhibition of ASF1A expression decreased embryonic development and increased DNA damages. Overexpression of ASF1A improved the developmental potential and decreased DNA damages. When 293 T cells that had been integrated with RGS-NHEJ were co-transfected with plasmids of pcDNA3.1-ASF1A, gRNA-NHEJ and hCas9, less cells expressed eGFP, indicating that non-homologous end joining (NHEJ) was reduced by ASF1A. When 293 T cells were co-transfected with plasmids of HR-donor, gRNA-HR, hCas9 and pcDNA3.1-ASF1A, more cells expressed eGFP, indicating that homologous recombination (HR) was enhanced by ASF1A. These results indicate that ASF1A may be associated with the genome stability maintenance of early mouse embryos and this action may be mediated by promoting DNA damage repair through HR pathway.

中文翻译：

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抗沉默因子 1A 与小鼠植入前胚胎的基因组稳定性维持相关†。

基因组稳定性对于植入前胚胎的正常发育至关重要，因为 DNA 损伤可能导致突变甚至胚胎致死。抗沉默因子 1A (ASF1A) 是一种组蛋白伴侣，在 MII 卵母细胞中作为母源因子富集，可能与维持基因组稳定性有关。因此，本研究旨在探索 ASF1A 在维持早期小鼠胚胎基因组稳定性中的作用。ASF1A 在植入前胚胎中表达，并在整个早期胚胎发育过程中显示出动态模式。抑制 ASF1A 表达会降低胚胎发育并增加 DNA 损伤。ASF1A 的过表达提高了发育潜力并减少了 DNA 损伤。当293个整合了RGS-NHEJ的T细胞与pcDNA3.1-ASF1A质粒共转染时，gRNA-NHEJ 和 hCas9，较少的细胞表达 eGFP，表明 ASF1A 减少了非同源末端连接 (NHEJ)。当 293 T 细胞与 HR 供体、gRNA-HR、hCas9 和 pcDNA3.1-ASF1A 质粒共转染时，更多细胞表达 eGFP，表明 ASF1A 增强了同源重组 (HR)。这些结果表明 ASF1A 可能与早期小鼠胚胎的基因组稳定性维持有关，并且该作用可能是通过 HR 途径促进 DNA 损伤修复来介导的。