Table 1

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

Receptor	Motif	Sequence	Gene	Reference
		`——▸ ——▸`
PPAR/RXR	DR-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/RXR	DR-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/RXR	DR-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).