| RRC ID |
39387
|
| 著者 |
Yamamoto H, Miyamoto K, Li B, Taketani Y, Kitano M, Inoue Y, Morita K, Pike JW, Takeda E.
|
| タイトル |
The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine.
|
| ジャーナル |
J Bone Miner Res
|
| Abstract |
The actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are mediated through the nuclear vitamin D receptor (VDR). The regulation of VDR abundance plays an important role in determining the magnitude of the target cell response to 1,25(OH)2D3. The major physiological activity of 1,25(OH)2D3 is the regulation of calcium absorption in the small intestine, and the level of VDR is an important factor in this regulation. However, the characterization of VDR gene expression in the small intestine remains unknown. In the present study, we investigated the regulation of the human VDR (hVDR) gene expression in the small intestine. The 4.0 kb of the 5'-flanking region of the hVDR gene promoter was cloned and characterized by the measurement of luciferase activity and an electrophoretic mobility-shift assay (EMSA). With the EMSA, we found that Cdx-2 (a homeodomain protein-related caudal) binds to the sequence 5'-ATAAAAACTTAT-3' at -3731 to -3720 bp (hVD-SIF1) relative to the transcription start site of the hVDR promoter. This sequence is very similar to the human sucrase-isomaltase footprint 1 (SIF1) element. With a competition analysis and specific antibodies for Cdx-2, we demonstrated that Cdx-2 is able to activate VDR gene transcription by binding to this element. The mutation of the hVD-SIF1 sequence in the hVDR gene promoter markedly suppressed the transactivation of the reporter gene in Caco-2 cells. In addition, the DNA fragment (-3996 to -3286) containing the hVD-SIF1 binding site increased transcription when placed upstream of the herpes simplex virus thymidine kinase promoter. These findings suggest that Cdx-2 plays an important role in the intestine-specific transcription of the hVDR gene.
|
| 巻・号 |
14(2)
|
| ページ |
240-7
|
| 公開日 |
1999-2-1
|
| DOI |
10.1359/jbmr.1999.14.2.240
|
| PMID |
9933478
|
| MeSH |
Animals
Base Sequence
Binding Sites / genetics
CDX2 Transcription Factor
Caco-2 Cells
Cell Line
DNA / genetics
DNA / metabolism
Female
Gene Expression Regulation
Gene Expression Regulation, Developmental
Genes, Reporter
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Intestine, Small / growth & development
Intestine, Small / metabolism*
Luciferases / genetics
Male
Molecular Sequence Data
Pregnancy
Promoter Regions, Genetic
Rats
Receptors, Calcitriol / genetics*
Tissue Distribution
Trans-Activators
Transcriptional Activation
Transfection
|
| IF |
5.854
|
| 引用数 |
119
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539)
Hep G2(RCB0459) |
