Reproductive success relies on a healthy oocyte competent for fertilisation and capable of sustaining early embryo development. By the end of oogenesis, the oocyte is characterised by a transcriptionally silenced state, but the significance of this state and how it is achieved remains poorly understood. Histone H3.3, one of the H3 variants, has unique functions in chromatin structure and gene expression that are cell cycle-independent. We report here a comprehensive characterisation of the roles of the subunits of the Hira complex (i.e. Hira, Cabin1 and Ubn1), which is primarily responsible for H3.3 deposition during mouse oocyte development. Loss-of-function of any component of the Hira complex led to early embryogenesis failure. Transcriptome and nascent RNA analyses revealed that mutant oocytes fail to silence global transcription. Hira complex mutants are unable to establish the H3K4me3 and H3K9me3 repressive marks, resulting in aberrant chromatin accessibility. Among the misregulated genes in mutant oocytes is Zscan4, a 2-cell specific gene that is involved in zygote genome activation. Overexpression of Zscan4 recapitulates the phenotypes of Hira mutants, illustrating that temporal and spatial expression of Zscan4 is fine-tuned at the oocyte-to-embryo transition. Thus, the H3.3 chaperone Hira complex has a maternal effect function in oocyte developmental competence and early embryogenesis by modulating chromatin condensation and transcriptional quiescence.

中文翻译：

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H3.3伴侣Hira复合物协调卵母细胞发育能力

生殖成功取决于健康的卵母细胞，能够受精并且能够维持早期胚胎发育。到卵子形成结束时，卵母细胞的特征是转录沉默状态，但对该状态的重要性及其实现方式的了解仍然很少。H3变体之一的组蛋白H3.3在染色质结构和基因表达中具有独特的功能，与细胞周期无关。我们在这里报告了Hira复合体（即Hira，Cabin1和Ubn1）的亚基的作用的全面表征，该亚基主要负责小鼠卵母细胞发育期间的H3.3沉积。Hira复合体任何成分的功能丧失导致早期胚胎发生失败。转录组和新生RNA分析表明，突变卵母细胞无法使整体转录沉默。Hira复合突变体无法建立H3K4me3和H3K9me3阻遏性标记，导致染色质的异常可及性。在突变卵母细胞中被错误调节的基因是Zscan4，这是一种2细胞特异性基因，与合子基因组激活有关。Zscan4的过表达概括了Hira突变体的表型，说明Zscan4的时空表达在卵母细胞到胚胎的过渡过程中是微调的。因此，H3.3分子伴侣Hira复合物通过调节染色质浓缩和转录静止在卵母细胞发育能力和早期胚胎发生中具有母体作用。2细胞特异性基因，参与合子基因组激活。Zscan4的过表达概括了Hira突变体的表型，说明Zscan4的时空表达在卵母细胞到胚胎的过渡过程中是微调的。因此，H3.3分子伴侣Hira复合物通过调节染色质浓缩和转录静止在卵母细胞发育能力和早期胚胎发生中具有母体作用。2细胞特异性基因，参与合子基因组激活。Zscan4的过表达概括了Hira突变体的表型，说明Zscan4的时空表达在卵母细胞到胚胎的过渡过程中是微调的。因此，H3.3分子伴侣Hira复合物通过调节染色质浓缩和转录静止在卵母细胞发育能力和早期胚胎发生中具有母体作用。