Characterization of xenobiotic responsive elements upstream from the drug-metabolizing cytochrome p-450c gene: A similarity to glucocorticoid regulatory elements

Atsuko Fujisawa-Sehara, Kazuhiro Sogawa, Miyuki Yamane, Yoshiaki Fujii-Kuriyama

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    277 Citations (Scopus)

    Abstract

    The DNA element governing the inducible expression of drug-metabolizing P-450c gene by xenobiotic treatments was investigated by gene transfer methods. A variety of dissected fragments from -844 to -1140bp region which was essential for the inducibility of P-450c gene were placed on the hetero-logous SV40 promoter for testing the inducibility. Mapping studies in combination with gel retardation assay defined the presence of the two xenobiotic responsive elements(XRE, XRE1, -1007 - -1021bp; XRE2, -1088 - -1092bp) composed of about 15 nucleotides which expressed the enhancer activity in response to xenobiotic inducers. The two XREs share 10 nucleotides in common out of 15 as expressed in the sequence CG/CTG/CC/TTG/CTCACGCT/AA and are arranged in the inverse orientation. They are different from DREs(drug responsive element) proposed previously(Sogawa, K. et al. Proc. Natl. Acad. Sci. 83, 8044-8048(1986)) and expressed a strong enhancer activity in response to 3-methylcholanthrene. The XRE shows a significant homology with glucocort.icoid regulatory elements and apparently needs normal functions of a putative xenobiotic receptor for the inducible enhancer activity.

    Original languageEnglish
    Pages (from-to)4179-4191
    Number of pages13
    JournalNucleic acids research
    Volume15
    Issue number10
    DOIs
    Publication statusPublished - 1987 May 26

    ASJC Scopus subject areas

    • Genetics

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