論文 - 詳細
| RRC ID | 38638 |
|---|---|
| 著者 | Hayashi S, Watanabe J, Kawajiri K. |
| タイトル | Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. |
| ジャーナル | 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. |
| 巻・号 | 110(4) |
| ページ | 559-65 |
| 公開日 | 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 |
| 引用数 | 581 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 6.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB0459) |