TY - JOUR
T1 - A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor-Arnt heterodimer
AU - Sogawa, Kazuhiro
AU - Numayama-Tsuruta, Keiko
AU - Takahashi, Tomohiro
AU - Matsushita, Natsuki
AU - Miura, Chisa
AU - Nikawa, Jun Ichi
AU - Gotoh, Osamu
AU - Kikuchi, Yasuo
AU - Fujii-Kuriyama, Yoshiaki
N1 - Funding Information:
This work was supported in part by a Grants-in-Aids for Scientific Research of priority areas from the Ministry of Education, Culture, Sports and Science of Japan, and by funds for Research for the Future Program of the Japan Society for Promotion of Science.
PY - 2004/6/4
Y1 - 2004/6/4
N2 - 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.
AB - 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.
KW - Ah receptor
KW - Arnt
KW - CYP1A2
KW - Coactivator
KW - Enhancer
KW - Inducible expression
KW - Xenobiotic response
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U2 - 10.1016/j.bbrc.2004.04.090
DO - 10.1016/j.bbrc.2004.04.090
M3 - Article
C2 - 15144902
AN - SCOPUS:2442549839
SN - 0006-291X
VL - 318
SP - 746
EP - 755
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -