Major zygotic genome activation (ZGA) occurs at the late 2‐cell stage and involves the activation of thousands of genes, supporting early embryonic development. The reasons underlying the regulation of ZGA are not clear. Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the nucleosome remodelling and histone deacetylation (NuRD) complex. Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late 2‐cell stage to the 8‐cell stage. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2‐cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate, and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2‐cell embryo revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomic data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B‐deficient 2‐cell embryos exhibited abnormalities in ZGA during the maternal‐to‐embryonic transition, with lower expression of the major ZGA marker MERVL. Overall, our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating ZGA.

中文翻译：

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GATAD2B 通过调节合子基因组激活是植入前胚胎发育所必需的

主要合子基因组激活（ZGA）发生在 2 细胞阶段晚期，涉及数千个基因的激活，支持早期胚胎发育。 ZGA 监管的原因尚不清楚。组蛋白尾部的乙酰化修饰促进转录激活，而 H4K16ac 的母体缺失会导致 ZGA 失败。 GATAD2B 是核小体重塑和组蛋白脱乙酰化 (NuRD) 复合物的核心亚基之一。我们的研究表明，GATAD2B 从 2 细胞阶段晚期到 8 细胞阶段表现出特异性的细胞核定位和高蛋白表达。这个有趣的现象促使我们研究 GATAD2B 和 ZGA 之间的关系。我们发现了 GATAD2B 的独特模式，从晚期 2 细胞阶段开始进行核定位。 GATAD2B 缺失导致胚胎发育缺陷，包括桑葚胚 DNA 损伤增加、囊胚形成率降低以及 ICM/TE 谱系分化异常。与卵裂阶段的延迟一致，2 细胞胚胎的转录组分析揭示了细胞周期 G2/M 相转变途径的抑制。此外，GATAD2B 蛋白质组数据提供了 GATAD2B 与参与细胞周期途径的分子之间存在某种关联的明确证据。正如假设的那样，GATAD2B 缺陷的 2 细胞胚胎在母体到胚胎的转变过程中表现出 ZGA 异常，主要 ZGA 标志物 MERVL 的表达较低。总的来说，我们的结果表明 GATAD2B 对于早期胚胎发育至关重要，部分是通过促进 ZGA 实现的。