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• W2110374722 endingPage "525" @default.
• W2110374722 startingPage "514" @default.
• W2110374722 abstract "Two vital enzymes of the CYP3A subfamily, CYP3A4 and CYP3A5, are differentially expressed in the human lung. However, the molecular mechanisms that regulate tissue-selective expression of the genes are poorly understood. The ability of the 5′ upstream promoter region of these two genes to drive luciferase reporter activities in human lung A549 cells was dramatically different. The <i>CYP3A5</i> promoter region activated luciferase gene expression by 10-fold over the promoterless construct, whereas the <i>CYP3A4</i> promoter did not drive expression. Sequence comparisons of the promoters identified a 57-base pair insertion in the <i>CYP3A4</i> promoter region (–71 to –127) that was absent in the <i>CYP3A5</i> promoter. Deletion of the 57-bp motif from <i>CYP3A4</i> or insertion into the <i>CYP3A5</i> promoter, showed that this motif represses <i>CYP3A4</i> expression in lung. EMSA analysis using nuclear extracts from either A549 cells or human lung tissues showed two specific protein/DNA complexes formed with the ³²P-labeled CYP3A4 57-bp oligonucleotide. EMSA analyses identified two E-box motifs as the minimal specific <i>cis</i>-elements. Supershift assays with antibodies directed against known double- or single-E-box binding factors (TAL1, δEF1, E2A, HEB, etc.) failed to identify this factor as a previously characterized <i>trans</i>-acting double E-box binding protein. These results demonstrated that the 5′-upstream region of <i>CYP3A4</i> contains an active putative double E-box repressor motif, not present in the 5′-upstream region of the <i>CYP3A5</i> gene, that attenuates <i>CYP3A4</i> expression in the human lung. We believe that this is the first documented case in which a cytochrome P450 gene is actively repressed in a tissue-specific manner." @default.
• W2110374722 created "2016-06-24" @default.
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• W2110374722 date "2007-06-04" @default.
• W2110374722 modified "2023-09-23" @default.
• W2110374722 title "Transcription Factor Binding to a Putative Double E-Box Motif Represses <i>CYP3A4</i> Expression in Human Lung Cells" @default.
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• W2110374722 doi "https://doi.org/10.1124/mol.106.033795" @default.
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