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

A. R. Shakoori, Andre J van Wijnen, R. Bortell, T. A. Owen, J. L. Stein, J. B. Lian, G. S. Stein

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)218-229
Number of pages12
JournalJournal of Cellular Biochemistry
Volume55
Issue number2
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Calcitriol Receptors
Osteocalcin
Osteoblasts
Osteosarcoma
Vitamin D
Transcription Factors
Genes
Proteins
Nijmegen Breakage Syndrome
DNA
Diploidy
Retinoid X Receptors
Methylation
Transcription
Sedimentation
Crosslinking
Pore size
Bone
Steroids
Association reactions

Keywords

  • Osteoblasts
  • Osteocalcin gene
  • Osteosarcoma cells
  • Transcription
  • Vitamin D response element (VDRE)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cells. / Shakoori, A. R.; van Wijnen, Andre J; Bortell, R.; Owen, T. A.; Stein, J. L.; Lian, J. B.; Stein, G. S.

In: Journal of Cellular Biochemistry, Vol. 55, No. 2, 1994, p. 218-229.

Research output: Contribution to journalArticle

Shakoori, A. R. ; van Wijnen, Andre J ; Bortell, R. ; Owen, T. A. ; Stein, J. L. ; Lian, J. B. ; Stein, G. S. / Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cells. In: Journal of Cellular Biochemistry. 1994 ; Vol. 55, No. 2. pp. 218-229.
@article{8da210e66a7f42c5b4c0dcd299c4b987,
title = "Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cells",
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.",
keywords = "Osteoblasts, Osteocalcin gene, Osteosarcoma cells, Transcription, Vitamin D response element (VDRE)",
author = "Shakoori, {A. R.} and {van Wijnen}, {Andre J} and R. Bortell and Owen, {T. A.} and Stein, {J. L.} and Lian, {J. B.} and Stein, {G. S.}",
year = "1994",
doi = "10.1002/jcb.240550209",
language = "English (US)",
volume = "55",
pages = "218--229",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cells

AU - Shakoori, A. R.

AU - van Wijnen, Andre J

AU - Bortell, R.

AU - Owen, T. A.

AU - Stein, J. L.

AU - Lian, J. B.

AU - Stein, G. S.

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

KW - Osteoblasts

KW - Osteocalcin gene

KW - Osteosarcoma cells

KW - Transcription

KW - Vitamin D response element (VDRE)

UR - http://www.scopus.com/inward/record.url?scp=0028283872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028283872&partnerID=8YFLogxK

U2 - 10.1002/jcb.240550209

DO - 10.1002/jcb.240550209

M3 - Article

C2 - 8089197

AN - SCOPUS:0028283872

VL - 55

SP - 218

EP - 229

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 2

ER -