論文 - 詳細
| RRC ID | 42677 |
|---|---|
| 著者 | Hashimoto K, Yamada M, Matsumoto S, Monden T, Satoh T, Mori M. |
| タイトル | Mouse sterol response element binding protein-1c gene expression is negatively regulated by thyroid hormone. |
| ジャーナル | Endocrinology |
| Abstract |
Sterol regulatory element-binding protein (SREBP)-1c is a key regulator of fatty acid metabolism and plays a pivotal role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis. In previous studies, the regulation of SREBP-1c mRNA levels by thyroid hormone has remained controversial. In this study, we examined whether T3 regulates the mouse SREBP-1c mRNA expression. We found that T3 negatively regulates the mouse SREBP-1c gene expression in the liver, as shown by ribonuclease protection assays and real-time quantitative RT-PCR. Promoter analysis with luciferase assays using HepG2 and Hepa1-6 cells revealed that T3 negatively regulates the mouse SREBP-1c gene promoter (-574 to +42) and that Site2 (GCCTGACAGGTGAAATCGGC) located around the transcriptional start site is responsible for the negative regulation by T3. Gel shift assays showed that retinoid X receptor-alpha/thyroid hormone receptor-beta heterodimer bound to Site2, but retinoid X receptor-alpha/liver X receptor- heterodimer could not bind to the site. In vivo chromatin immunoprecipitation assays demonstrated that T3 induced thyroid hormone receptor-beta recruitment to Site2. Thus, we demonstrated that mouse SREBP-1c mRNA is down-regulated by T3 in vivo and that T3 negatively regulates mouse SREBP-1c gene transcription via a novel negative thyroid hormone response element: Site2. |
| 巻・号 | 147(9) |
| ページ | 4292-302 |
| 公開日 | 2006-9-1 |
| DOI | 10.1210/en.2006-0116 |
| PII | en.2006-0116 |
| PMID | 16794015 |
| MeSH | Animals Base Sequence Carcinoma, Hepatocellular Cell Line Cell Line, Tumor Chlorocebus aethiops Down-Regulation / drug effects Gene Deletion Gene Expression Regulation / drug effects* Humans Kidney Liver / chemistry Liver Neoplasms Male Mice Mice, Inbred C57BL Molecular Sequence Data Mutagenesis Promoter Regions, Genetic / genetics RNA, Messenger / analysis Receptors, Thyroid Hormone / metabolism Response Elements / genetics Retinoid X Receptors / metabolism Reverse Transcriptase Polymerase Chain Reaction Sterol Regulatory Element Binding Protein 1 / genetics* Transcription, Genetic / drug effects Transfection Triiodothyronine / pharmacology* |
| IF | 3.934 |
| 引用数 | 52 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | Hepa 1-6(RCB1638) |