Regulation of basal core promoter activity of human organic cation transporter 1 (OCT1/SLC22A1)
| العنوان: | Regulation of basal core promoter activity of human organic cation transporter 1 (OCT1/SLC22A1) |
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| المؤلفون: | Toshiya Katsura, Moto Kajiwara, Jun-ichi Asaka, Masayo Aoki, Iwao Ikai, Tomohiro Terada, Ken-ichi Inui |
| المصدر: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 295:G1211-G1216 |
| بيانات النشر: | American Physiological Society, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Physiology, DNA Mutational Analysis, Molecular Sequence Data, E-box, Biology, Polymorphism, Single Nucleotide, E-Box Elements, Transactivation, Cell Line, Tumor, Physiology (medical), Transcriptional regulation, Humans, Electrophoretic mobility shift assay, Promoter Regions, Genetic, Transcription factor, Regulation of gene expression, Base Sequence, Hepatology, General transcription factor, Gastroenterology, Promoter, Molecular biology, Gene Expression Regulation, Hepatocyte Nuclear Factor 4, Upstream Stimulatory Factors, Transcription Initiation Site, Octamer Transcription Factor-1 |
| الوصف: | Human organic cation transporter 1 (OCT1/SLC22A1) plays important roles in the hepatic uptake of cationic drugs. The functional characteristics of this transporter have been well evaluated, but molecular information regarding transcriptional regulation is limited. In the present study, therefore, we examined the gene regulation of OCT1 gene focusing on basal core expression. An ∼2.5-kb fragment of the OCT1 promoter region was isolated, and promoter activity was measured by luciferase assay in the human liver cell lines Huh7 and HepG2. Deletion analysis suggested that the region spanning −141/−69 was essential for the basal core transcriptional activity and that this region contained the sequence of a cognate E-box (CACGTG). The E-box is known to be bound by the basal transcription factors, upstream stimulating factors (USFs), and the functional involvements of USF1 and USF2 were confirmed by a transactivation effect, a mutational analysis of the E-box, and an electrophoretic mobility shift assay. The transactivation effect of USFs on the OCT1 promoter was further stimulated by hepatocyte nuclear factor 4α, a liver-enriched transcription factor. There were no polymorphisms in the proximal promoter region (about 400 bp) of OCT1 gene ( n = 109). These findings indicated that both USF1 and USF2 bind to an E-box sequence located in the OCT1 core promoter region and are required for the basal gene expression of this transporter. |
| تدمد: | 1522-1547 0193-1857 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e686caa4e999ed2f3ec87d6d7ba23431 https://doi.org/10.1152/ajpgi.90360.2008 |
| رقم الأكسشن: | edsair.doi.dedup.....e686caa4e999ed2f3ec87d6d7ba23431 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221547 01931857 |
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