Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, University, MS 38677, United States.
Environ Toxicol Pharmacol. 2013 Jul;36(1):40-50. doi: 10.1016/j.etap.2013.02.014. Epub 2013 Feb 28.
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 24μg/L from 2.5 to 96hpf 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.
DNA 甲基化对于基因调控很重要,并且容易受到生命早期环境污染物的影响。我们发现,斑马鱼胚胎在 2.5 到 96 小时暴露于 24μg/L 的直接水基苯并[a]芘中,其全球胞嘧啶甲基化水平显著降低了 44.8%,vasa 基因启动子甲基化水平降低了 17%。结果,vasa 的表达显著增加了 33%。相比之下,环境相关浓度的苯并[a]芘暴露并未改变癌症基因如 ras 相关结构域家族成员 1(rassf1)、端粒酶逆转录酶(tert)、c-jun 和 c-myca 中的 CpG 岛甲基化或基因表达。同样,苯并[a]芘也没有改变 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 活性没有受到影响,但 GNMT 酶活性适度增加。总之,苯并[a]芘是一种表观遗传修饰剂,可改变斑马鱼幼虫的整体和特定基因的 DNA 甲基化状态。