kdm4aa knockout disturbs early embryonic development in Zebrafish via downregulating rbm46.

IF 1.7 4区 生物学 Q4 CELL BIOLOGY
Zygote Pub Date : 2026-02-01 Epub Date: 2026-03-09 DOI:10.1017/S0967199425100257
Hui Jiang, Xinqing Cai, Rui Deng, Jiamin Wang, Hongkuan Song, Weiran Chai, Bingshe Han, Junfang Zhang
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引用次数: 0

Abstract

Histone lysine-specific demethylase 4A (KDM4A) plays a critical role in the embryonic development of mammals such as mouse and goat, however its function in zebrafish (Danio rerio) embryogenesis remains poorly understood, due to the existence of two kdm4a paralogs (kdm4aa and kdm4ab) in zebrafish. The current study revealed that kdm4aa-/- embryos exhibited dramatically increased mortality during gastrulation. RT-qPCR showed that RNA-binding motif protein 46 (rbm46) was downregulated after kdm4aa knockout. CUT&Tag-qPCR revealed that kdm4aa knockout significantly decreased H3K4me3, while increasing H3K9me3 and H3K36me3 at rbm46 promoter. kdm4aa-/- embryos displayed elevated reactive oxygen species (ROS) and reduced adenosine triphosphate (ATP). And rbm46 mRNA injection alleviated ROS accumulation and increased ATP level, thereby rescuing the lethal phenotype in kdm4aa-/- embryos. Our findings demonstrate that kdm4aa knockout disturbs zebrafish embryogenesis by suppressing rbm46 mRNA expression.

敲除kdm4aa通过下调rbm46干扰斑马鱼早期胚胎发育。
组蛋白赖氨酸特异性去甲基化酶4A (KDM4A)在小鼠和山羊等哺乳动物的胚胎发育中起着至关重要的作用,但由于在斑马鱼中存在两种KDM4A类似物(kdm4aa和kdm4ab),因此对其在斑马鱼(Danio rerio)胚胎发生中的功能知之甚少。目前的研究表明,kdm4aa-/-胚胎在原肠胚形成过程中表现出显著增加的死亡率。RT-qPCR结果显示,敲除kdm4aa后,rna结合基序蛋白46 (rbm46)下调。CUT&Tag-qPCR结果显示,敲除kdm4aa显著降低了H3K4me3,而在rbm46启动子处增加了H3K9me3和H3K36me3。kdm4aa-/-胚胎显示活性氧(ROS)升高,三磷酸腺苷(ATP)减少。注射rbm46 mRNA可减轻kdm4aa-/-胚胎的ROS积累,提高ATP水平,从而挽救kdm4aa-/-胚胎的致死表型。我们的研究结果表明,敲除kdm4aa通过抑制rbm46 mRNA的表达来干扰斑马鱼的胚胎发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Zygote
Zygote 生物-发育生物学
CiteScore
1.70
自引率
5.90%
发文量
117
审稿时长
6-12 weeks
期刊介绍: An international journal dedicated to the rapid publication of original research in early embryology, Zygote covers interdisciplinary studies on gametogenesis through fertilization to gastrulation in animals and humans. The scope has been expanded to include clinical papers, molecular and developmental genetics. The editors will favour work describing fundamental processes in the cellular and molecular mechanisms of animal development, and, in particular, the identification of unifying principles in biology. Nonetheless, new technologies, review articles, debates and letters will become a prominent feature.
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