Xenobiotic responsive element in the 5'-upstream region of the human P-450c gene

Momoyo Kubota, Kazuhiro Sogawa, Yoshiko Kaizu, Takuji Sawaya, Junko Watanabe, Kaname Kawajiri, Osamu Gotoh, Yoshiaki Fujii-kuriyama

    Research output: Contribution to journalArticlepeer-review

    55 Citations (Scopus)

    Abstract

    The nucleotide sequence of the 5'-upstream region up to about -4.1 kb of the human P-460c gene was determined. Two kinds of repetitive sequences were located; one was the Alu sequence which was inserted at three positions (-3127 to -3038, -3017 to -2770, and -2167 to -1851), and the other was the SINE-R element located just upstream of the most distal Alu sequences. The region other than the two repeated sequences showed an overall similarity of 70% to that of the rat P-450c gene. Survey of XRE or its homologues, responsible for the inducible expression of the rat P-450c gene, revealed eight XRE core sequences in this region of the human P-460c gene. Three of them were carried in the Alu sequences. A fusion gene which was constructed by ligating the upstream region of the human P-460c gene to the chloramphenicol acetyltransferase (CAT) gene expressed the CAT activity in response to the inducer, methylcholanthrene, when transfected into Hepa-1 cells. Stepwise decrease in CAT activity in three regions was observed as the 5 -upstream sequence containing XRE motifs was removed. However, the XRE core sequence in the Alu sequences seemed inactive, because elimination of the three elements in the Alu sequences did not affect the expressed CAT activity. In accordance with this observation, competition experiments using gel mobility shift assay showed that XRE core sequences in the Alu sequences could not compete with the XRE sequence for the inducer-bound receptor. Other XRE motifs than those in the Alu sequences appeared active and were conserved at similar positions to their counterparts in the rat P-450c gene.

    Original languageEnglish
    Pages (from-to)232-236
    Number of pages5
    JournalJournal of biochemistry
    Volume110
    Issue number2
    DOIs
    Publication statusPublished - 1991 Aug

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology

    Fingerprint Dive into the research topics of 'Xenobiotic responsive element in the 5'-upstream region of the human P-450c gene'. Together they form a unique fingerprint.

    Cite this