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

  • Feng Wang , Shengli Shi , Ruixue Zhang and Oliver Hankinson
Published/Copyright: September 14, 2006
Biological Chemistry
From the journal Volume 387 Issue 9

Abstract

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 1α, 2α and 3α, 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.

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References

Antonsson, C., Arulampalam, V., Whitelaw, M.L., Pettersson, S., and Poellinger, L. (1995). Constitutive function of the basic helix-loop-helix/PAS factor Arnt. J. Biol. Chem.270, 13968–13972.10.1074/jbc.270.23.13968Search in Google Scholar

Bruick, R.K. (2000). Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA97, 9082–9087.10.1073/pnas.97.16.9082Search in Google Scholar

Cherry, S.R., Biniszkiewicz, D., van Parijs, L., Baltimore, D., and Jaenisch, R. (2000). Retroviral expression in embryonic stem cells and hematopoietic stem cells. Mol. Cell. Biol.20, 7419–7426.10.1128/MCB.20.20.7419-7426.2000Search in Google Scholar

Hankinson, O. (1979). Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc. Natl. Acad. Sci. USA76, 373–376.10.1073/pnas.76.1.373Search in Google Scholar

Hankinson, O. (2002). Aryl hydrocarbon receptor nuclear translocator (Arnt) [hypoxia inducible factor β (HIF-1β)]. In: Wiley Encyclopedia of Molecular Medicine Vol. 5 (Hoboken, USA: John Wiley & Sons, Inc.), pp. 265–266.Search in Google Scholar

Huffman, J.L., Mokashi, A., Bächinger, H.P., and Brennan, R.G. (2001). The basic helix-loop-helix domain of the aryl hydrocarbon receptor nuclear transporter (ARNT) can oligomerize and bind E-Box DNA specifically. J. Biol. Chem.276, 40537–40544.10.1074/jbc.M105675200Search in Google Scholar

Li, C. and Wong, W.H. (2003). DNA-Chip Analyzer (dChip). In: The Analysis of Gene Expression Data: Methods and Software, G. Parmigiani, E.S. Garrett, R. Irizarry and S.L. Zeger, eds. (New York, USA: Springer), pp. 120–141.10.1007/0-387-21679-0_5Search in Google Scholar

Li, H., Dong, L., and Whitlock, J.P. Jr. (1994). Transcriptional activation function of the mouse Ah receptor nuclear translocator. J. Biol. Chem.269, 28098–28105.10.1016/S0021-9258(18)46900-1Search in Google Scholar

Numayama-Tsuruta, K., Kobayashi, A., Sogawa, K., and Fujii-Kuriyama, Y. (1997). A point mutation responsible for defective function of the aryl-hydrocarbon-receptor nuclear translocator in mutant Hepa-1c1c7 cells. Eur. J. Biochem.246, 486–495.10.1111/j.1432-1033.1997.00486.xSearch in Google Scholar PubMed

Probst, M.R., Reisz-Porszasz, S., Agbunag, R.V., Ong, M.S., and Hankinson, O. (1993). Role of the aryl hydrocarbon receptor nuclear translocator protein in aryl hydrocarbon (dioxin) receptor action. Mol. Pharmacol.44, 511–518.Search in Google Scholar

Seidel, S.D. and Denison, M.S. (1999). Differential gene expression in wild-type and arnt-defective mouse hepatoma (Hepa1c1c7) cells. Toxicol. Sci.52, 217–225.10.1093/toxsci/52.2.217Search in Google Scholar PubMed

Sogawa, K., Nakano, R., Kobayashi, A., Kikuchi, Y., Ohe, N., Matsushita, N., and Fujii-Kuriyama, Y. (1995). Possible function of Ah receptor nuclear translocator (Arnt) homodimer in transcriptional regulation. Proc. Natl. Acad. Sci. USA92, 1936–1940.10.1073/pnas.92.6.1936Search in Google Scholar PubMed PubMed Central

Vadigepalli, R., Chakravarthula, P., Zak, D.E., Schwaber, J.S., and Gonye, G.E. (2003). PAINT: a promoter analysis and interaction network generation tool for gene regulatory network identification. OMICS7, 235–252.10.1089/153623103322452378Search in Google Scholar PubMed

Zhang, J., Watson, A.J., Probst, M.R., Minehart, E., and Hankinson, O. (1996). Basis for the loss of aryl hydrocarbon receptor gene expression in clones of a mouse hepatoma cell line. Mol. Pharmacol.50, 1454–1462.Search in Google Scholar

Published Online: 2006-09-14
Published in Print: 2006-09-01

©2006 by Walter de Gruyter Berlin New York

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