The H3.3 chaperone Hira complex orchestrates oocyte developmental competence.
The H3.3 chaperone Hira complex orchestrates oocyte developmental competence.
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DOI：
10.1242/dev.200044
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发表时间：
2022-03-01
期刊：
影响因子：
--
通讯作者：
Lin CJ
中科院分区：
文献类型：
--
作者：
Smith R;Susor A;Ming H;Tait J;Conti M;Jiang Z;Lin CJ
成功的生殖需要一个有能力维持早期胚胎发育的卵母细胞。卵子发生结束时，卵母细胞进入转录沉默状态，其机制和意义仍然知之甚少。组蛋白H3.3是组蛋白H3的变体，在染色质结构和基因表达方面具有独特的细胞周期独立功能。在这里，我们已经表征了H3.3分子伴侣Hira/Cabin 1/Ubn 1复合物，表明这些亚基中的任何一个的功能丧失都会导致小鼠早期胚胎发生失败。转录组和新生RNA分析表明，转录异常沉默突变卵母细胞。组蛋白标记，包括H3 K4 me 3和H3 K9 me 3，在Hira/Cabin 1突变体中减少，染色质可及性受损。突变卵母细胞中的失调基因包括Zscan 4d，一种参与合子基因组激活的两细胞特异性基因。Zscan 4在卵母细胞中的过表达部分地再现了Hira突变体的表型，并且在Cabin 1突变体卵母细胞中Zscan 4敲低部分地恢复了它们的发育潜力，说明Zscan 4的时间和空间表达在卵母细胞到胚胎的过渡中被微调。因此，H3.3分子伴侣Hira复合物通过调节染色质凝聚和转录静止，在卵母细胞发育能力和胚胎发生中具有母体效应功能。总结：H3.3分子伴侣Hira复合物通过调节染色质凝聚和转录静止在卵母细胞发育能力和胚胎发生中具有母体效应功能。
Successful reproduction requires an oocyte competent to sustain early embryo development. By the end of oogenesis, the oocyte has entered a transcriptionally silenced state, the mechanisms and significance of which remain poorly understood. Histone H3.3, a histone H3 variant, has unique cell cycle-independent functions in chromatin structure and gene expression. Here, we have characterised the H3.3 chaperone Hira/Cabin1/Ubn1 complex, showing that loss of function of any of these subunits causes early embryogenesis failure in mouse. Transcriptome and nascent RNA analyses revealed that transcription is aberrantly silenced in mutant oocytes. Histone marks, including H3K4me3 and H3K9me3, are reduced and chromatin accessibility is impaired in Hira/Cabin1 mutants. Misregulated genes in mutant oocytes include Zscan4d, a two-cell specific gene involved in zygote genome activation. Overexpression of Zscan4 in the oocyte partially recapitulates the phenotypes of Hira mutants and Zscan4 knockdown in Cabin1 mutant oocytes partially restored their developmental potential, 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 embryogenesis, through modulating chromatin condensation and transcriptional quiescence. Summary: The H3.3 chaperone Hira complex has a maternal effect function in oocyte developmental competence and embryogenesis by modulating chromatin condensation and transcriptional quiescence.
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影响因子：
64.5
作者：
Banaszynski LA;Wen D;Dewell S;Whitcomb SJ;Lin M;Diaz N;Elsässer SJ;Chapgier A;Goldberg AD;Canaani E;Rafii S;Zheng D;Allis CD
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
7.7
作者：
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