AhR regulates the expression of human cytochrome P450 1A1 (CYP1A1) by recruiting Sp1.


Journal

The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646

Informations de publication

Date de publication:
11 2019
Historique:
received: 19 12 2018
revised: 09 04 2019
accepted: 11 06 2019
pubmed: 15 6 2019
medline: 12 6 2020
entrez: 15 6 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31199573
doi: 10.1111/febs.14956
doi:

Substances chimiques

AHR protein, human 0
Basic Helix-Loop-Helix Transcription Factors 0
Carcinogens 0
Receptors, Aryl Hydrocarbon 0
Sp1 Transcription Factor 0
SP1 protein, human 0
CYP1A1 protein, human EC 1.14.14.1
Cytochrome P-450 CYP1A1 EC 1.14.14.1

Banques de données

GENBANK
['NM_000499', 'NM_138473', 'NM_001621']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4215-4231

Subventions

Organisme : Department of Education of Guangdong Province
ID : 2017KCXTD001
Pays : International
Organisme : Natural Science Foundation of Guangdong Province
ID : 2015A030312005
Pays : International
Organisme : Science and Technology Program of Guangzhou
ID : 201804020067
Pays : International
Organisme : Science and Technology Program of Guangzhou
ID : 201607010177
Pays : International

Informations de copyright

© 2019 Federation of European Biochemical Societies.

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Auteurs

Wenchu Ye (W)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Ruohong Chen (R)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Xiaoxuan Chen (X)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Boyan Huang (B)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Ruqin Lin (R)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Xuan Xie (X)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Jiongjie Chen (J)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Jun Jiang (J)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Yiqun Deng (Y)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

Jikai Wen (J)

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University Guangzhou, Guangzhou, Guangdong, 510642, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

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