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首页> 外文期刊>Journal of biochemical and molecular toxicology >Selective cytochrome P450 1A1 but not 1B1 promoterCpG island DNA methylation by 6-formylindolo[3,2-b]carbazole (FICZ)
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Selective cytochrome P450 1A1 but not 1B1 promoterCpG island DNA methylation by 6-formylindolo[3,2-b]carbazole (FICZ)

机译：选择性细胞色素P450 1A1但不是1B1促进突出岛DNA甲基化甲基吲哚[3,2-B]咔唑（FICZ）

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摘要

Epigenetic alterations are essential for normal mammalian development and regulation of gene expression. In this study, we aimed to determine if an enigmatic endogenous ligand of the aryl hydrocarbon receptor (AHR), 6-formylindolo[3,2-b] carbazole (FICZ), and methionine (Meth) have an epigenetic impact on AHR-regulated cytochrome P450 1A1 and B1 (CYP1A1 and CYP1B1) gene expression. Human hepatoma (HepG2-XRE-Luc and huh7) cells were exposed to FICZ in a medium with and without Meth supplementation. Selective and transient silencing of CYP1A1 but not CYP1B1 were seen by FICZ. Here we found that FICZ transiently represses CYP1A1 by targeting DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and concomitant DNA methylation of the CYP1A1 promoter gene. Treatments with 5-aza-dC augmented CYP1A1 transcription activity. Our results reveal a new mechanism for transient activation of AHR by FICZ that can negatively and positively influence gene expression, and highlight the regulatory role of Meth on the CYP1A1 gene expression.
机译：表观遗传学改变对哺乳动物的正常发育和基因表达调控至关重要。在本研究中，我们旨在确定芳香烃受体（AHR）、6-甲酰吲哚[3,2-b]咔唑（FICZ）和蛋氨酸（Meth）的神秘内源性配体是否对AHR调节的细胞色素P450 1A1和B1（CYP1A1和CYP1B1）基因表达有表观遗传学影响。将人肝癌（HepG2 XRE-Luc和huh7）细胞暴露于FICZ培养基中，添加和不添加冰毒。FICZ观察到CYP1A1而非CYP1B1的选择性和瞬时沉默。在这里，我们发现FICZ通过靶向DNA（胞嘧啶-5）-甲基转移酶3A（DNMT3A）和伴随的CYP1A1启动子基因的DNA甲基化来短暂抑制CYP1A1。5-氮杂-dC处理可增强CYP1A1转录活性。我们的结果揭示了FICZ短暂激活AHR的新机制，该机制可以对基因表达产生负面和正面影响，并强调了Meth对CYP1A1基因表达的调节作用。

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