setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals.
setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals.
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setd2 敲除斑马鱼是可行且可繁殖的：不同脊椎动物中 Setd2 和组蛋白 H3K36 三甲基化的差异和发育应激相关要求。
DOI：
10.1038/s41421-020-00203-8
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发表时间：
2020
期刊：
影响因子：
33.5
通讯作者：
Sun XJ
中科院分区：
文献类型：
--
作者：
Liu DJ;Zhang F;Chen Y;Jin Y;Zhang YL;Chen SB;Xie YY;Huang QH;Zhao WL;Wang L;Xu PF;Chen Z;Chen SJ;Li B;Zhang A;Sun XJ
Setd 2是催化组蛋白H3赖氨酸36三甲基化（H3 K36 me 3）的唯一酶，几乎所有活跃转录的蛋白质编码基因，这种机制是进化保守的从酵母到人类。尽管有这种广泛和保守的活性，Setd 2和H3 K36 me 3是酵母正常生长所必需的，但对于哺乳动物胚胎发生（如小鼠卵母细胞成熟和胚胎血管发生）是绝对必需的，这就提出了一个问题，即Setd 2在特定发育阶段的功能需求是如何通过进化出现的。本文通过研究Setd 2在斑马鱼中的重要性和功能来探讨这一问题。令人惊讶的是，setd 2-null斑马鱼是可行的和肥沃的。它们表现出孟德尔出生率和正常胚胎发生，没有在小鼠中观察到的血管缺陷;然而，它们具有归因于能量代谢和蛋白质合成不足的小体型表型，这是以营养依赖的方式可逆的。与无菌的Setd 2缺失小鼠不同，Setd 2缺失斑马鱼可以产生功能性精子和卵母细胞。尽管如此，与小鼠卵母细胞成熟所需的母体Setd 2相关，不携带母体Setd 2的第二代setd 2缺失斑马鱼显示出存活率降低和母体到合子过渡的发育延迟。综上所述，这些结果表明，虽然setd 2缺失的斑马鱼和小鼠的表型明显不同，但它们是平行匹配的，因为潜在的机制是进化保守的。因此，Setd 2的差异性要求可能反映了与生物体通过发育所经历的内在和/或外在压力相关的不同生存力阈值，并且这些表观遗传调节机制可能作为支持生命从简单到复杂进化的保留来源。
Setd2 is the only enzyme that catalyzes histone H3 lysine 36 trimethylation (H3K36me3) on virtually all actively transcribed protein-coding genes, and this mechanism is evolutionarily conserved from yeast to human. Despite this widespread and conserved activity, Setd2 and H3K36me3 are dispensable for normal growth of yeast but are absolutely required for mammalian embryogenesis, such as oocyte maturation and embryonic vasculogenesis in mice, raising a question of how the functional requirements of Setd2 in specific developmental stages have emerged through evolution. Here, we explored this issue by studying the essentiality and function of Setd2 in zebrafish. Surprisingly, the setd2-null zebrafish are viable and fertile. They show Mendelian birth ratio and normal embryogenesis without vascular defect as seen in mice; however, they have a small body size phenotype attributed to insufficient energy metabolism and protein synthesis, which is reversable in a nutrition-dependent manner. Unlike the sterile Setd2-null mice, the setd2-null zebrafish can produce functional sperms and oocytes. Nonetheless, related to the requirement of maternal Setd2 for oocyte maturation in mice, the second generation of setd2-null zebrafish that carry no maternal setd2 show decreased survival rate and a developmental delay at maternal-to-zygotic transition. Taken together, these results indicate that, while the phenotypes of the setd2-null zebrafish and mice are apparently different, they are matched in parallel as the underlying mechanisms are evolutionarily conserved. Thus, the differential requirements of Setd2 may reflect distinct viability thresholds that associate with intrinsic and/or extrinsic stresses experienced by the organism through development, and these epigenetic regulatory mechanisms may serve as a reserved source supporting the evolution of life from simplicity to complexity.
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影响因子：
5.8
作者：
Chu, S. Haihua;Chabon, Jonathan R.;Armstrong, Scott A.
通讯作者：
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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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20.3
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