Functional Analysis of the Dioxin Response Elements (DREs) of the Murine CYP1A1 Gene Promoter: Beyond the Core DRE Sequence

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Functional Analysis of the Dioxin Response Elements (DREs) of the Murine CYP1A1 Gene Promoter: Beyond the Core DRE Sequence
	Li, Shuaizhang ; Pei, Xinhui ; Zhang, Wen ; Xie, Heidi Qunhui ; Zhao, Bin
刊名	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
	2014
卷号	15 期号:4 页码:6475-6487
关键词	aryl hydrocarbon receptor (AhR) 2 dioxin responsive element (DRE) 3 7 8-tetrachlorodibenzo-p-dioxin (TCDD) transcriptional regulation
ISSN号	1422-0067
中文摘要	The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the biological and toxicological effects of halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). When activated by dioxin, the cytosolic AhR protein complex translocates into the nucleus and dimerizes with the ARNT (Ah receptor nuclear translocator) protein. The heteromeric ligand: AhR/Arnt complex then recognizes and binds to its specific DNA recognition site, the dioxin response element (DRE). DREs are located upstream of cytochrome P4501A1 (CYP1A1) and other AhR-responsive genes, and binding of the AhR complex stimulates their transcription. Although CYP1A1 expression has been used as the model system to define the biochemical and molecular mechanism of AhR action, there is still limited knowledge about the roles of each of the seven DREs located in the CYP1A1 promoter. These seven DREs are conserved in mouse, human and rat. Deletion analysis showed that a single DRE at -488 was enough to activate the transcription. Truncation analysis demonstrated that the DRE at site -981 has the highest transcriptional efficiency in response to TCDD. This result was verified by mutation analysis, suggesting that the conserved DRE at site -981 could represent a significant and universal AhR regulatory element for CYP1A1. The reversed substituted intolerant core sequence (5'-GCGTG-3' or 5'-CACGC-3') of seven DREs reduced the transcriptional efficiency, which illustrated that the adjacent sequences of DRE played a vital role in activating transcription. The core DRE sequence (5'-TNGCGTG-3') tends to show a higher transcriptional level than that of the core DRE sequence (5'-CACGCNA-3') triggered by TCDD. Furthermore, in the core DRE (5'-TNGCGTG-3') sequence, when "N" is thymine or cytosine (T or C), the transcription efficiency was stronger compared with that of the other nucleotides. The effects of DRE orientation, DRE adjacent sequences and the nucleotide "N" in the core DRE (5'-TNGCGTG-3') sequence on the AhR-regulated CYP1A1 transcription in response to TCDD were studied systematically, and our study laid a good foundation for further investigation into the AhR-dependent transcriptional regulation triggered by dioxin and dioxin-like compounds.
WOS记录号	WOS:000336841200085
公开日期	2015-03-24
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/9371]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Li, Shuaizhang,Pei, Xinhui,Zhang, Wen,et al. Functional Analysis of the Dioxin Response Elements (DREs) of the Murine CYP1A1 Gene Promoter: Beyond the Core DRE Sequence[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2014,15(4):6475-6487.
APA	Li, Shuaizhang,Pei, Xinhui,Zhang, Wen,Xie, Heidi Qunhui,&Zhao, Bin.(2014).Functional Analysis of the Dioxin Response Elements (DREs) of the Murine CYP1A1 Gene Promoter: Beyond the Core DRE Sequence.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,15(4),6475-6487.
MLA	Li, Shuaizhang,et al."Functional Analysis of the Dioxin Response Elements (DREs) of the Murine CYP1A1 Gene Promoter: Beyond the Core DRE Sequence".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 15.4(2014):6475-6487.