Benzo[a]pyrene decreases global and gene specific DNA methylation during zebrafish development.

Benzo[a]pyrene decreases global and gene specific DNA methylation during zebrafish development.
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DOI:
10.1016/j.etap.2013.02.014
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发表时间:
2013-07
影响因子:
4.3
通讯作者:
Willett KL
Willett KL
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Fang X;Thornton C;Scheffler BE;Willett KL

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DNA 甲基化对于基因调控很重要,并且很容易受到生命早期接触环境污染物的影响。我们发现,在受精后 (hpf) 2.5 至 96 小时内,斑马鱼胚胎直接暴露于 24 μg/L 的水性苯并[a]芘 (BaP) 可使整体胞嘧啶甲基化显着降低 44.8%,vasa 启动子甲基化显着降低 17%。因此,vasa 表达显着增加了 33%。相比之下,环境相关浓度的 BaP 暴露不会改变癌症基因中的 CpG 岛甲基化或基因表达,例如 ras 关联结构域家族成员 1 (rassf1)、端粒酶逆转录酶 (tert)、c-jun 和 c-myca。同样,BaP 不会改变 DNA 甲基转移酶 1 (dnmt1) 和甘氨酸 N-甲基转移酶 (gnmt) 的基因表达。虽然总 DNMT 活性未受影响,但 GNMT 酶活性适度增加。总之,BaP 是斑马鱼幼虫整体和基因特异性 DNA 甲基化状态的表观遗传修饰剂。
DNA methylation is important for gene regulation and is vulnerable to early-life exposure to environmental contaminants. We found that direct waterborne benzo[a]pyrene (BaP) exposure at 24 μg/L from 2.5 to 96 hours post fertilization (hpf) to zebrafish embryos significantly decreased global cytosine methylation by 44.8% and promoter methylation in vasa by 17%. Consequently, vasa expression was significantly increased by 33%. In contrast, BaP exposure at environmentally relevant concentrations did not change CpG island methylation or gene expression in cancer genes such as ras-association domain family member 1 (rassf1), telomerase reverse transcriptase (tert), c-jun, and c-myca. Similarly, BaP did not change gene expression of DNA methyltransferase 1 (dnmt1) and glycine N-methyltransferase (gnmt). While total DNMT activity was not affected, GNMT enzyme activity was moderately increased. In summary, BaP is an epigenetic modifier for global and gene specific DNA methylation status in zebrafish larvae.
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