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Sogawa, K. et al.

Sogawa, Numayama-Tsuruta, Takahashi, Matsushita, Miura, Nikawa, Gotoh, Kikuchi, Fujii-Kuriyama,

A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor- Arnt heterodimer.

We have identified an enhancer responsible for induction by 3-methylcholanthrene in the upstream region of the CYP1A2 gene. The enhancer does not contain the invariant core sequence of XREs that are binding sites for the Ah receptor ( AhR) and Arnt heterodimer. The enhancer did not show any inducible expression in Hepa-1-derived cell lines, C4 and C12, deficient of Arnt and AhR, respectively. On the other hand, bacterially expressed AhR- Arnt heterodimer could not bind to the enhancer. Mutational analysis of the enhancer revealed that a repeated sequence separated by six nucleotides is important for expression. A factor binding specifically to the enhancer was found by using gel shift assays. Bacterially expressed AhR- Arnt heterodimer interacted with the factor. A dominant negative mutant of the AhR to XRE activated the enhancer. Collectively, these results demonstrate that a novel induction mechanism is present in which the AhR- Arnt heterodimer functions as a coactivator.[1]

References

A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor-Arnt heterodimer. Sogawa, K., Numayama-Tsuruta, K., Takahashi, T., Matsushita, N., Miura, C., Nikawa, J., Gotoh, O., Kikuchi, Y., Fujii-Kuriyama, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]

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