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Feng Wang, Shengli Shi, Ruixue Zhang, Oliver Hankinson

Identifying target genes of the aryl hydrocarbon receptor nuclear translocator (Arnt) using DNA microarray analysis

Keywords: aryl hydrocarbon receptor nuclear translocator (Arnt), bHLH-PAS, DNA microarray, target genes

The aryl hydrocarbon receptor nuclear translocator (Arnt) is a basic helix-loop-helix (bHLH) protein that also contains a Per-Arnt-Sim (PAS) domain. In addition to forming heterodimers with many other bHLH-PAS proteins, including the aryl hydrocarbon receptor (AhR) and hypoxia-inducible factors 1?, 2? and 3?, Arnt can also form homodimers when expressed from its cDNA in vitro or in vivo. However, target genes of the Arnt/Arnt homodimer remain to be identified. In this study, we have elucidated the profile of genes responsive to the reintroduction of Arnt expression in an Arnt-deficient mouse hepatoma cell line (c4), using DNA microarray analysis. The expression of 27 genes was upregulated by 1.5-fold or more in c4 cells infected with a retroviral vector expressing mouse Arnt, while no genes were found to be downregulated. Among the upregulated genes, BCL2/adenovirus E1B 19 kDa-interacting protein 1 (NIP3), serine (or cysteine) proteinase inhibitor, clade E, member 1 (PAI1), and N-myc downstream regulated-like (NDR1), were confirmed to be induced by Arnt using real-time PCR. We also found that the 5? promoter region of 15 out of 20 upregulated genes contain the type 2 E-box 5?-CACGTG-3? Arnt/Arnt binding sequence, consistent with the notion that they represent target genes for Arnt.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 387, 09/2006
Pages: 1215 - 1218

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