GSBS Student Publications

Title

Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cells

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology; Department of Medicine, Diabetes Division

Date

6-1-1994

Document Type

Article

Medical Subject Headings

Animals; Base Sequence; DNA; Gene Expression Regulation; Molecular Sequence Data; Osteoblasts; Osteocalcin; Osteosarcoma; Phosphorylation; Promoter Regions (Genetics); Rats; Receptors, Calcitriol; Receptors, Cytoplasmic and Nuclear; *Receptors, Retinoic Acid; Retinoid X Receptors; *Transcription Factors; Transcription, Genetic; Tumor Cells, Cultured; Vitamin D

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Vitamin D responsive transcription of the bone-specific osteocalcin gene differs markedly in osteosarcoma cells and normal diploid osteoblasts. In osteoblasts the osteocalcin gene is transcribed, and upregulated by Vitamin D, only in post-proliferative cells, but in osteosarcoma cells expression is constitutive. This distinction in transcriptional regulation of the osteocalcin gene correlates with striking differences in the relative representation of two principal Vitamin D-dependent protein/DNA complexes designated V1 and V2 at the Vitamin D responsive element in the osteocalcin promoter. Formation of both complexes is Vitamin D dependent and they contain the Vitamin D receptor as well as an RXR related protein. Pore size exclusion and sedimentation velocity analyses suggest that the V1 and V2 complexes represent oligomeric protein assemblies (respectively, tetramers and trimers), and reflect primarily DNA-directed association of the monomeric protein components at the osteocalcin Vitamin D responsive element. UV crosslinking and methylation interference analyses of the V1 and V2 complexes at the osteocalcin Vitamin D responsive element indicate differences in protein/DNA recognition. For example, the V1 complex interacts with both steroid half-elements, whereas the V2 complex appears to recognize the proximal half-element. Our findings suggest variations in protein/protein and protein/DNA interactions of the VDR and RXR related complexes V1 and V2 at the osteocalcin Vitamin D responsive element that reflect unique properties of the osteosarcoma and normal diploid osteoblast phenotype.

Rights and Permissions

Citation: J Cell Biochem. 1994 Jun;55(2):218-29. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Journal of cellular biochemistry

PubMed ID

8089197