Format

Send to

Choose Destination
See comment in PubMed Commons below
J Bone Miner Res. 1999 Feb;14(2):240-7.

The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine.

Author information

1
Department of Clinical Nutrition, School of Medicine, University of Tokushima, Tokushima, Japan.

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.

PMID:
9933478
DOI:
10.1359/jbmr.1999.14.2.240
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center