| RRC ID |
42677
|
| Author |
Hashimoto K, Yamada M, Matsumoto S, Monden T, Satoh T, Mori M.
|
| Title |
Mouse sterol response element binding protein-1c gene expression is negatively regulated by thyroid hormone.
|
| Journal |
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.
|
| Volume |
147(9)
|
| Pages |
4292-302
|
| Published |
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
|
| Times Cited |
52
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| Human and Animal Cells |
Hepa 1-6(RCB1638) |
