DNA methylation and gene expression alterations in zebrafish embryos exposed to cadmium
DNA methylation and gene expression alterations in zebrafish embryos exposed to cadmium
复制标题
镉暴露斑马鱼胚胎 DNA 甲基化和基因表达变化
DOI：
10.1007/s11356-021-12691-6
复制
发表时间：
2021-02-13
影响因子：
5.8
通讯作者：
Gao, Yongfei
中科院分区：
文献类型：
--
作者：
Bian, Xiaoxue;Gao, Yongfei
一个未被探索的Cd毒性的分子机制是对表观遗传机制的干扰，如DNA甲基化，这一过程对胎儿早期发育至关重要。为了研究Cd对金属硫蛋白（MT）和金属硫蛋白（Dnmts）转录本、DNA甲基化标记物和信号通路基因表达的影响，将斑马鱼胚胎在受精后24小时（最大8细胞期开始）暴露于0.0089、0.089和0.89 μM Cd环境中。结果表明，在12 hpf后，斑马鱼胚胎中的Cd积累量达到稳定水平；不同浓度组间各时间点Cd累积量差异显著。MT mRNA折叠率与胚胎Cd含量呈极显著正相关。我们发现，0.089 μM Cd暴露组DNA甲基转移酶（Dnmts）表达水平显著上调。在0.89 μM Cd暴露组，dnmt1表达显著上调，dnmt3表达和整体甲基化水平显著下调。Cd上调derbb -3基因表达，下调derbb -4基因表达，中和derbb -1基因表达。Cd激活了ca2 +、MAPK-JUK、p38 MAPkinase、PI3K-AKT和vegf信号通路基因，表明这些通路基因与Cd暴露水平相关。该结果有助于阐明金属胁迫下斑马鱼胚胎DNA甲基化的分子机制，并进一步干扰表观遗传机制。
An unexplored attributing molecular mechanism of Cd toxicity is interference with the epigenetic machinery, such as DNA methylation, processes that are crucial for early fetal development. In order to investigate the effects of Cd on the expression of metallothionein (MT) and Dnmts transcripts, markers of DNA methylation, and signaling pathway gene expression, zebrafish embryos were exposed during 24 hours post-fertilization (starting at maximum 8-cell stage) to 0.0089, 0.089, and 0.89 μM Cd. The results showed that the Cd accumulation in zebrafish embryo reached a stable level after 12 hpf, and the Cd accumulation at individual time points was significantly different among different concentration groups. MT mRNA fold was significantly positive with the Cd content in embryos. We observed that the expression level of DNA methyltransferase (Dnmts) in the 0.089 μM Cd exposure group was significantly up-regulated.Dnmt1expression was significantly up-regulated in the 0.89 μM Cd exposure group, andDnmt3sexpression and global methylation levels were significantly down-regulated. Cd up-regulatedErbB-3gene expression, down-regulatedErbB-4gene expression, and neutralizedErbB-1gene expression. Cd activatedCa2+,MAPK-JUK,p38 MAPkinase,PI3K-AKT, andVEGFsignaling pathway genes, indicating these pathway genes related to Cd exposure level. The results are helpful to clarify the molecular mechanism of DNA methylation in zebrafish embryo under metal pressure and further interference with the epigenetic machinery.