Dynamic Alterations in DNA Methylation Precede Tris(1,3-dichloro-2-propyl)phosphate-Induced Delays in Zebrafish Epiboly,Environmental Science & Technology Letters

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Dynamic Alterations in DNA Methylation Precede Tris(1,3-dichloro-2-propyl)phosphate-Induced Delays in Zebrafish Epiboly
Environmental Science & Technology Letters ( IF 8.9 ) Pub Date : 2017-08-15 00:00:00 , DOI: 10.1021/acs.estlett.7b00332
Allison Kupsco ₁ , Subham Dasgupta ₁ , Christine Nguyen ₁ , David C. Volz ₁

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Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphate flame retardant that impacts zebrafish epiboly, an effect that may be associated with genomewide hypomethylation. Using zebrafish as a model, the objectives of this study were (1) to quantify concentration-dependent impacts of TDCIPP on epiboly, (2) to determine whether co-exposure with folic acid (FA), a methyl donor, mitigates TDCIPP-induced impacts, and (3) using 10 previously identified TDCIPP-susceptible loci, to rely on bisulfite amplicon sequencing (BSAS) to monitor CpG methylation dynamics across multiple TDCIPP concentrations in the presence or absence of FA. Embryos were exposed to TDCIPP from 0.75 h postfertilization (hpf) to 2, 4, 6, or 24 hpf in the presence or absence of 1 mM FA. Although TDCIPP delayed epiboly by up to 3 h by 6 hpf and induced malformations by 24 hpf, FA was unable to mitigate TDCIPP-induced effects at any stage that was evaluated. Moreover, while no differences in global methylation were detected using a 5-methylcytosine DNA enzyme-linked immunosorbent assay, BSAS revealed that TDCIPP-induced effects on CpG methylation were dependent on concentration and developmental stage and that early effects on methylation do not persist despite continuous exposure. Our findings demonstrate that TDCIPP delays zebrafish epiboly, a phenotype that is preceded by complex, dynamic alterations in DNA methylation.

中文翻译：

DNA甲基化的动态变化先于三（1,3-二氯-2-丙基）磷酸引起的斑马鱼外延延迟。

磷酸三（1,3-二氯-2-丙基）酯（TDCIPP）是一种有机磷酸酯阻燃剂，可影响斑马鱼的外突，这种作用可能与全基因组低甲基化有关。以斑马鱼为模型，这项研究的目的是（1）量化TDCIPP对依皮的浓度依赖性影响，（2）确定与甲基供体叶酸（FA）的共同暴露是否减轻了TDCIPP诱导的（3）使用10个先前确定的TDCIPP易感基因座，依靠亚硫酸氢盐扩增子测序（BSAS）在有或没有FA的情况下跨多个TDCIPP浓度监测CpG甲基化动力学。在存在或不存在1 mM FA的情况下，将胚胎从受精后0.75 h（hpf）暴露于Tcpipp，2、4、6或24 hpf。尽管TDCIPP外延最多延迟3 h达6 hpf，诱导畸形最多延迟24 hpf，但FA在任何评估的阶段均无法减轻TDCIPP诱导的影响。此外，虽然使用5-甲基胞嘧啶DNA酶联免疫吸附试验未检测到总体甲基化的差异，但BSAS显示TDCIPP诱导的CpG甲基化作用取决于浓度和发育阶段，尽管持续存在，对甲基化的早期作用仍未持续接触。我们的发现表明，TDCIPP延缓了斑马鱼的外延，这种表型先于DNA甲基化的复杂，动态改变。虽然使用5-甲基胞嘧啶DNA酶联免疫吸附试验未检测到总体甲基化的差异，但BSAS显示TDCIPP诱导的CpG甲基化作用取决于浓度和发育阶段，尽管持续暴露，对甲基化的早期作用仍未持续。我们的发现表明，TDCIPP延缓了斑马鱼的外延，这种表型先于DNA甲基化的复杂，动态改变。虽然使用5-甲基胞嘧啶DNA酶联免疫吸附试验未检测到总体甲基化的差异，但BSAS显示TDCIPP诱导的CpG甲基化作用取决于浓度和发育阶段，尽管持续暴露，对甲基化的早期作用仍未持续。我们的发现表明，TDCIPP延缓了斑马鱼的外延，这种表型先于DNA甲基化的复杂，动态改变。

更新日期：2017-08-15

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