Rabbit prostaglandin omega-hydroxylase (CYP4A4): gene structure and expression.
Genomic DNA containing the entire gene encoding P450 4A4, a cytochrome P450 that is elevated during pregnancy, was isolated on two overlapping recombinant phage. The isolated gene, CYP4A4, encodes a protein that differs at one amino acid position from the predicted sequence of a previously isolated cDNA. The intron/exon structure is highly conserved in relation to the clofibrate inducible genes CYP4A1, CYP4A2, and CYP4A6. However, the 5' flanking sequences of these genes exhibit little identity. Two transcriptional start sites of the CYP4A4 gene have been determined by RNase protection analysis and are located 37 and 40 nucleotides upstream of the initiation codon. Like other CYP4A genes the CYP4A4 promoter does not contain a TATA consensus sequence. CYP4A4 mRNAs are not detected in the lungs, liver, and kidneys of untreated rabbits by RNase protection assays. However, CYP4A4 mRNA is present to varying degrees in all three of these tissues during pregnancy with the greatest abundance observed in the lung and the lowest in the kidney. Treatment of male rabbits with dexamethasone also increases the levels of CYP4A4 mRNA in the lung and liver, but the levels are eightfold less than those seen for pregnant rabbits. Consensus recognition sequences for either the glucocorticoid or progesterone receptors were not found in 1086 bp of sequence upstream of the start of transcription.
Palmer
C N
CN
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Griffin
K J
KJ
Johnson
E F
EF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002994:Clofibrate / Q000494:pharmacology; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005091:Exons; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015698:Genomic Library; D007438:Introns; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box; D014158:Transcription, Genetic
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C026961:prostaglandin omega hydroxylases; D002994:Clofibrate