High temperature induced masculinization of zebrafish by down-regulation of sox9b and esr1 via DNA methylation
High temperature induced masculinization of zebrafish by down-regulation of sox9b and esr1 via DNA methylation
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DOI：
10.1016/j.jes.2021.01.032
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发表时间：
2021-09-01
影响因子：
6.9
通讯作者：
Huang, Dejun
中科院分区：
文献类型：
--
作者：
Han, Jiangyuan;Hu, Yan;Huang, Dejun
温度升高可能通过改变鱼类性别相关基因的表达而影响鱼类的性别分化。然而，基因表达改变的潜在机制仍然知之甚少。本研究旨在探讨DNA甲基化在斑马鱼性别分化中的作用。结果表明，与正常温度（28摄氏度）相比，受精后20至30天（dpf）的高温（33摄氏度）暴露导致雄性偏向的性别比例，以及cyp 19 a1 a，sox 9 b和esr 1等雌性相关基因的表达下降。同时，DNA甲基转移酶dnmt 3a 1和dnmt 3a 2的表达以及sox 9 b和esr 1启动子的DNA甲基化水平均显著升高，表明DNA甲基化参与了高温诱导的斑马鱼雄性化过程。5-aza-2 '-deoxycytidine（DNA甲基化抑制剂）的共同处理减弱了高温诱导的斑马鱼雄性化效应，恢复了esr 1和sox 9 b的表达，抑制了dnmt 3a 1和dnmt 3a 2的转录，降低了esr 1和sox 9 b启动子的甲基化，进一步证实了DNA甲基化在高温诱导的斑马鱼雄性化中起重要作用。此外，sox 9 b启动子甲基化降低了转录因子CREB（cAMP反应元件结合蛋白）的富集。总之，这些研究结果表明，高温诱导斑马鱼雄性化的雌性相关基因通过DNA甲基化下调，提供了一个新的见解，在理解热介导的性别分化的表观遗传机制在鱼类。(c)2021中国科学院生态环境科学研究中心由爱思唯尔公司出版
Elevated temperature could influence the sex differentiation by altering the expression of sex-related genes in fish. However, the underlying mechanisms by which the gene expression is altered remain poorly understood. Here, we aimed to explore the role of DNA methylation in sex differentiation of zebrafish (Danio rerio) in response to elevated temperature. The results showed that high temperature (33 degrees C) exposure of fish from 20 to 30 days post fertilization (dpf), compared to normal temperature (28 degrees C), resulted in male-biased sex ratio and decreased expression of female-related genes including cyp19a1a, sox9b and esr1. Meanwhile, the expressions of DNA methyltransferases dnmt3a1 and dnmt3a2, and the DNA methylation levels in sox9b and esr1 promoter were significantly increased by high temperature, strongly implying that DNA methylation is involved in high temperature-induced masculinization of zebrafish. Co-treatment with 5-aza-2'-deoxycytidine (a DNA methylation inhibitor) attenuated the high temperature-induced masculinizing effect, recovered the expression of esr1 and sox9b, suppressed the transcription of dnmt3a1 and dnmt3a2, and decreased the methylation of esr1 and sox9b promoter, further confirming that DNA methylation plays an important role in high temperature-induced masculinization of zebrafish. Furthermore, the methylation of sox9b promoter decreased the enrichment of transcription factor CREB (cAMP-responsive element binding proteins). Overall, these findings suggest that high temperature induce masculinization of zebrafish by down-regulation of female-related genes via DNA methylation, providing a new insight in understanding the epigenetic mechanism of thermal-mediated sex differentiation in fish. (c) 2021 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.