USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.

USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.
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卵母细胞成熟过程中 USP16 介导的组蛋白 H2A 赖氨酸 119 去泛素化是合子基因组激活的先决条件

DOI:
10.1093/nar/gkac468
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发表时间:
2022-06-10
影响因子:
14.9
通讯作者:
Sha, Qian-Qian
Sha, Qian-Qian
中科院分区:
生物学2区
文献类型:
--
作者:
Rong, Yan;Zhu, Ye-Zhang;Yu, Jia-li;Wu, Yun-Wen;Ji, Shu-Yan;Zhou, Yong;Jiang, Yu;Jin, Jin;Fan, Heng-Yu;Shen, Li;Sha, Qian-Qian

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母合子转换(MZT)是动物发育的第一步,也是关键的一步,与染色质结构的变化和组蛋白修饰密切相关。H2AK119ub1是调节染色质构型和功能的重要表观遗传修饰,主要由PRC1催化,并有助于抵抗小鼠胚胎中的转录重编程。在这项研究中,H2AK119ub1在MZT小鼠全基因组的动态分布进行了研究,使用染色体免疫沉淀和测序。结果表明,H2AK119ub1积累在完全发育的卵母细胞和富集在母亲的基因的TSS,但迅速下降后减数分裂恢复在全基因组,包括早期合子基因的TSS,由以前未知的机制。遗传学证据表明,泛素特异性肽酶16(USP 16)是小鼠卵母细胞中H2AK 119 ub1的主要去泛素化酶。在卵母细胞中有条件地敲除Usp16并不损害它们的存活、生长或减数分裂成熟。然而,缺乏USP16的卵母细胞在受精后经历合子基因组激活或获得发育能力时存在缺陷,这可能与合子基因组上高水平的母体H2AK119ub1沉积有关。综上所述,H2AK119ub1水平在卵母细胞成熟过程中通过USP16依赖性机制下降,这确保了合子基因组重编程和必需的早期合子基因的转录激活。
Abstract Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.
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