| RRC ID |
38638
|
| Author |
Hayashi S, Watanabe J, Kawajiri K.
|
| Title |
Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene.
|
| Journal |
J Biochem
|
| Abstract |
We identified genetic polymorphisms in the 5'-flanking region of the human cytochrome P450IIE1 gene and investigated the effect of these polymorphisms on the transcriptional regulation of the gene. PCR direct sequencing of the two homozygous alleles [types A (c1/c1) and C (c2/c2)] revealed the existence of several point mutations in the distal 5'-flanking region of the gene, but no differences in the proximal promoter region. The DNA segment (-1372 to -960) placed upstream of SV40 promoter and the chloramphenicol acetyltransferase (CAT) gene enhanced the expression of the gene, and the enhancement of expression by type C DNA was about 10 times that by its type A counterpart. DNase I footprinting analysis showed at least one protected region in which one of the polymorphic loci (RsaI polymorphism) was located. The DNase I sensitivities and protection profiles of the two genotypes were different. The protected region had high homology to the consensus sequence of the binding region of liver specific transcription factor HNF1 (LF-B1), and this was confirmed by gel retardation assay. These results indicate that genetic polymorphisms in the 5'-flanking region of the human P450IIE1 gene affect its binding of trans-acting factor and change its transcriptional regulation. This may lead to inter-individual differences of microsomal drug oxidation activity.
|
| Volume |
110(4)
|
| Pages |
559-65
|
| Published |
1991-10-1
|
| DOI |
10.1093/oxfordjournals.jbchem.a123619
|
| PMID |
1778977
|
| MeSH |
Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Chloramphenicol O-Acetyltransferase / genetics
Chloramphenicol O-Acetyltransferase / metabolism
Cytochrome P-450 CYP2E1
Cytochrome P-450 Enzyme System / blood
Cytochrome P-450 Enzyme System / genetics*
DNA / blood
DNA / genetics
DNA / isolation & purification
DNA-Binding Proteins / metabolism
Deoxyribonuclease I
Gene Expression Regulation, Enzymologic*
Genotype
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte Nuclear Factor 1-beta
Humans
Molecular Sequence Data
Nuclear Proteins*
Oligonucleotide Probes
Oxidoreductases, N-Demethylating / blood
Oxidoreductases, N-Demethylating / genetics*
Polymerase Chain Reaction
Polymorphism, Genetic*
Rats
Restriction Mapping
Sequence Homology, Nucleic Acid
TATA Box
Transcription Factors / metabolism
Transcription, Genetic*
|
| IF |
2.476
|
| Times Cited |
581
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
Hep G2(RCB0459)
CACO-2(RCB0988) |
