Table 1

Nuclear receptor response elements in the 5′-flanking regions of P-450 genes

         ——▸   ——▸
PPAR/RXRDR-1 aactAGGGTA a AGTTCAgtg CYP4A1 Aldridge et al., 1995
aactAGGGCA a AGTTGAggg CYP4A6 Muerhoff et al., 1992
aagtAGGACA a AGGCCAggg CYP4A6 Muerhoff et al., 1992
        ——▸ tga ——▸
PXR/RXRDR-3 AGTTCA   AGTTCA CYP3A23 Quattrochi et al., 1995; Huss et al., 1996
      ◂——     ——▸
ER-6 agaataTGAACT caaagg AGGTCAgtgagt CYP3A4 Barwick et al., 1996
agaataTTAACT caatgg AGGTCAgtgagt CYP3A7 Pascussi et al., 1999
agcacaTGAACT cagagg AGGTCAccacgg CYP3A6 Barwick et al., 1996
agaatgTTAACT caaagg AGGTCAaaaata CYP3A23 Quattrochi et al., 1995; Huss et al. 1996
      ——▸        ——▸
CAR/RXRDR-4 gtgccaAGGTCA  ggaa  AGTACAgattct Cyp2b10 Honkakoski et al., 1998b
DR-4     gGTGTCA  ggca  AGTTGAggtgg Cyp2b10 Honkakoski et al., 1998b
DR-4    caAGGTCA  ggaa  AGTACAgt CYP2B6 Sueyoshi et al., 1999

Uppercase sequences are related to the hexameric consensus binding site for nuclear receptors, (A/G)(A/G)(G/T)TCA. The repeated motifs are either direct repeats (DR, arrows pointing in one direction) or everted repeats (ER, arrows pointing away from each other) separated by different numbers of spacer nucleotides (lowercase letter nucleotides). A DR-4 element is also present within the ER-6 motif of the CYP3A4 upstream regulatory region (bold) and was shown to bind CAR/RXR heterodimers (Sueyoshi et al., 1999). Genomic sequences originally designated as the cDNA CYP3A1 correspond more closely to the 5′ untranslated sequence of 3A23, and 3A23 mRNA is highly induced by DEX, whereas 3A1 and 3A2 mRNAs are not (Komori and Oda, 1994).