Role of DNA methylation of AHR1 and AHR2 promoters in differential sensitivity to PCBs in Atlantic Killifish, Fundulus heteroclitus.
Role of DNA methylation of AHR1 and AHR2 promoters in differential sensitivity to PCBs in Atlantic Killifish, Fundulus heteroclitus.
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DOI：
10.1016/j.aquatox.2010.10.010
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发表时间：
2011-01-17
影响因子：
4.5
通讯作者：
Hahn, Mark E.
中科院分区：
文献类型：
--
作者：
Aluru, Neelakanteswar;Karchner, Sibel I.;Hahn, Mark E.
栖息在新贝德福德港（美国马萨诸塞州）受多氯联苯污染的超级基金场地的大西洋鳉鱼（Fundulus heteroclitus）已经进化出对这些化合物毒性作用的遗传抗性。在暴露于AHR激动剂后，它们也缺乏细胞色素P4501 A（CYP 1A）和其他芳烃受体（AHR）依赖性反应的诱导，表明AHR信号通路的整体下调。在这项研究中，我们假设，遗传抗性是由于AHR基因的启动子区的DNA超甲基化导致的AHR表达改变栖息在新贝德福德港的鱼类。为了验证这一假设，我们克隆和测序AHR 1和AHR 2启动子区，并采用亚硫酸氢盐转化-聚合酶链反应（BS-PCR），然后克隆分析比较的CpG岛的AHR 1和AHR 2的成年？在NBH和SC鱼之间的AHR 1或AHR 2启动子区域中未观察到甲基化谱的显著差异。然而，在这两个人群中，AHR 1启动子的高甲基化与肝脏中转录本的低表达相关。与AHR 1相比，AHR 2的肝脏mRNA表达较高，其启动子低甲基化。总之，我们的研究结果表明，NBH鱼对污染物的遗传抗性不是由于AHR启动子区域的甲基化改变，而是启动子甲基化可能控制AHR基因在鳉鱼中的组织特异性表达。
Atlantic killifish (Fundulus heteroclitus) inhabiting the PCB-contaminated Superfund site in New Bedford Harbor (MA, USA) have evolved genetic resistance to the toxic effects of these compounds. They also lack induction of cytochrome P4501A (CYP1A) and other aryl hydrocarbon receptor (AHR)-dependent responses after exposure to AHR agonists, suggesting an overall down-regulation of the AHR signaling pathway. In this study, we hypothesized that the genetic resistance is due to altered AHR expression resulting from hypermethylation of DNA in the promoter region of AHR genes in fish inhabiting New Bedford Harbor. To test this hypothesis, we cloned and sequenced AHR1 and AHR2 promoter regions and employed bisulfite conversion-polymerase chain reaction (BS-PCR) followed by clonal analysis to compare the methylation status of CpG islands of AHR1 and AHR2 in livers of adult killifish collected from New Bedford Harbor and a reference site (Scorton Creek, MA). No significant differences in methylation profiles were observed in either AHR1 or AHR2 promoter regions between NBH and SC fish. However, hypermethylation of the AHR1 promoter correlated with low expression of transcripts in the liver in both populations. In comparison to AHR1, hepatic mRNA expression of AHR2 is high and its promoter is hypomethylated. Taken together, our results suggest that genetic resistance to contaminants in NBH fish is not due to altered methylation of AHR promoter regions, but that promoter methylation may control tissue-specific expression of AHR genes in killifish.
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影响因子：
4.8
作者：
Karchner, SI;Powell, WH;Hahn, ME
通讯作者：
Hahn, ME
影响因子：
4.5
作者：
Elskus, AA;Monosson, E;Woltering, DS
通讯作者：
Woltering, DS
影响因子：
2.4
作者：
Nacci, D;Coiro, L;Cooper, KR
通讯作者：
Cooper, KR
影响因子：
5.3
作者：
COOPER, DN;KRAWCZAK, M
通讯作者：
KRAWCZAK, M
影响因子：
3.8
作者：
Meyer, JN;Nacci, DE;Di Giulio, RT
通讯作者：
Di Giulio, RT