Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a]pyrene exposure.
Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a]pyrene exposure.
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苯并暴露后，对斑马鱼胚胎和幼虫中特定启动子DNA甲基化的影响。
DOI：
10.1016/j.cbpc.2014.02.005
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发表时间：
2014-06
影响因子：
3.9
通讯作者：
Willett, K. L.
中科院分区：
文献类型：
--
作者：
Corrales, J.;Fang, X.;Thornton, C.;Mei, W.;Barbazuk, W. B.;Duke, M.;Scheffler, B. E.;Willett, K. L.
苯并[a]芘（BaP）是一种公认的致癌物和生殖发育毒物。人类和动物接触苯并（a）芘与不育和多代健康后果有关。DNA甲基化是研究最多的调节基因表达的表观遗传机制，甲基化模式的定位已成为理解病理基因表达事件的重要工具。本研究的目的是调查在斑马鱼胚胎和幼体的启动子DNA甲基化的异常变化后，父母和继续胚胎水性苯并[a]芘曝光。总共选择了21个已知在人类疾病中起作用的基因，通过多重深度测序来测量甲基化百分比。在受精后96小时（hpf）与3.3 hpf相比，dazl、nqo 1、sox 3、cyp 1b 1和gstp 1具有更高的甲基化百分比，而c-fos和cdkn 1a具有降低的CG甲基化。苯并（a）芘暴露显著降低产卵量和后代存活率。此外，BaP降低了3.3和96 hpf的整体甲基化，并改变了CG，CHH和CHG甲基化。在3.3 hpf时，6个基因（c-fos、cdkn 1a、dazl、nqo 1、nrf 2和sox 3）和96 hpf时，10个基因（c-fos、cyp 1b 1、dazl、gstp 1、mlh 1、nqo 1、pten、p53、sox 2和sox 3）的CG甲基化因BaP而改变10%或更多。BaP还诱导cyp 1b 1和gstp 1在96 hpf时的基因表达，发现它们是高甲基化的。需要进一步的研究来将异常的CG、CHH和CHG甲基化与晚年疾病相关的可遗传表观遗传后果联系起来。
Benzo[a]pyrene (BaP) is an established carcinogen and reproductive and developmental toxicant. BaP exposure in humans and animals has been linked to infertility and multigenerational health consequences. DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and mapping of methylation patterns has become an important tool for understanding pathologic gene expression events. The goal of this study was to investigate aberrant changes in promoter DNA methylation in zebrafish embryos and larvae following a parental and continued embryonic waterborne BaP exposure. A total of 21 genes known for their role in human diseases were selected to measure percent methylation by multiplex deep sequencing. At 96 hours post fertilization (hpf) compared to 3.3 hpf, dazl, nqo1, sox3, cyp1b1, and gstp1 had higher methylation percentages while c-fos and cdkn1a had decreased CG methylation. BaP exposure significantly reduced egg production and offspring survival. Moreover, BaP decreased global methylation and altered CG, CHH, and CHG methylation both at 3.3 and 96 hpf. CG methylation changed by 10% or more due to BaP in six genes (c-fos, cdkn1a, dazl, nqo1, nrf2, and sox3) at 3.3 hpf and in ten genes (c-fos, cyp1b1, dazl, gstp1, mlh1, nqo1, pten, p53, sox2, and sox3) at 96 hpf. BaP also induced gene expression of cyp1b1 and gstp1 at 96 hpf which were found to be hypermethylated. Further studies are needed to link aberrant CG, CHH, and CHG methylation to heritable epigenetic consequences associated with disease in later life.
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