AhR regulates the expression of human cytochrome P450 1A1 (CYP1A1) by recruiting Sp1 机翻标题: 暂无翻译,请尝试点击翻译按钮。

来源
The FEBS journal
年/卷/期
2019 / 286 / 21
页码
4215-4231
ISSN号
1742-464X
作者单位
South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;South China Agr Univ Guangzhou, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou 510642, Guangdong, Peoples R China;
作者
Chen, Ruohong;Chen, Xiaoxuan;Huang, Boyan;Lin, Ruqin;Xie, Xuan;Chen, Jiongjie;Jiang, Jun;Deng, Yiqun;Ye, Wenchu;Wen, Jikai;
摘要
Cytochrome P450 1A1 (CYP1A1) is abundant in the kidney, liver, and intestine and is involved in the phase I metabolism of numerous endogenous and exogenous compounds. Therefore, exploring the regulatory mechanism of its basal expression in humans is particularly important to understand the bioactivation of several procarcinogens to their carcinogenic derivatives. Site-specific mutagenesis and deletion of the transcription factor binding site determined the core cis-acting elements in the human CYP1A1 proximal and distal promoter regions. The proximal promoter region [overlapping xenobiotic-responsive element (XRE) and GC box sequences] determined the basal expression of CYP1A1. In human hepatocellular carcinoma cells (HepG2) with aryl hydrocarbon receptor (AhR) or specificity protein 1 (Sp1) knockdown, we confirmed that AhR and Sp1 are involved in basal CYP1A1 expression. In HepG2 cells overexpressing either AhR or Sp1, AhR determined the proximal transactivation of basal CYP1A1 expression. Via DNA affinity precipitation assays and ChIP, we found that AhR bound to the promoter and recruited Sp1 to transactivate CYP1A1 expression. The coordinated interaction between Sp1 and AhR was identified to be DNA mediated. Our work revealed a basal regulatory mechanism of an interesting human gene by which AhR interacts with Sp1 through DNA and recruits Sp1 to regulate basal CYP1A1 expression.
机翻摘要
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关键词/主题词
basal expression;coordinated regulation;GC box;XRE;
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