Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression

R. Bortell, T. A. Owen, Joseph Bidwell, P. Gavazzo, E. Breen, A. J. Van Wijnen, H. F. Deluca, J. L. Stein, J. B. Lian, G. S. Stein

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The observation that vitamin D-mediated enhancement of osteocalcin (OC) gene expression is dependent on and reciprocally related to the level of basal gene expression suggests that an interaction of the vitamin D responsive element (VDRE) with basal regulatory elements of the OC gene promoter contributes to both basal and vitamin D-enhanced transcription. Protein-DNA interactions at the VDRE of the rat OC gene (nucleotides -466 to -437) are reflected by direct sequence-specific and antibody-sensitive binding of the endogenous vitamin D receptor present in ROS 17/2.8 osteosarcoma nuclear protein extracts. In addition, a vitamin D-responsive increase in OC gene transcription is accompanied by enhanced non-vitamin D receptor-mediated protein-DNA interactions in the "TATA" box region (nucleotides -44 to +23), which also contains a potential glucocorticoid responsive element. Evidence for proximity of the VDRE with the basal regulatory elements is provided by two features of nuclear architecture. (i) Nuclear matrix attachment elements in the rat OC gene promoter that bind nuclear matrix proteins with sequence specificity may impose structural constraints on promoter conformation. (ii) Limited micrococcal nuclease digestion and Southern blot analysis indicate that three nucleosomes can be accommodated in the sequence spanning the OC gene VDRE, the OC/CCAAT box (nucleotides -99 to -76), and the TATA/glucocorticoid responsive element, and thereby the potential distance between the VDRE and the basal regulatory elements can be reduced. A model is presented for the contribution of both the VDRE and proximal promoter elements to the enhancement of OC gene transcription in response to vitamin D. The vitamin D receptor plus accessory proteins may function cooperatively with basal regulatory factors to modulate the extent to which the OC gene is transcribed.

Original languageEnglish (US)
Pages (from-to)6119-6123
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number13
StatePublished - Jul 1 1992
Externally publishedYes

Fingerprint

Osteocalcin
Vitamin D
Gene Expression
DNA
Proteins
Genes
Calcitriol Receptors
Nucleotides
Glucocorticoids
Nuclear Matrix-Associated Proteins
Micrococcal Nuclease
Nuclear Matrix
TATA Box
Nucleosomes
Osteosarcoma
Nuclear Proteins
Southern Blotting
Digestion
Antibodies

Keywords

  • Differentiation
  • Gene regulation
  • Hormone
  • Osteoblasts
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression. / Bortell, R.; Owen, T. A.; Bidwell, Joseph; Gavazzo, P.; Breen, E.; Van Wijnen, A. J.; Deluca, H. F.; Stein, J. L.; Lian, J. B.; Stein, G. S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 13, 01.07.1992, p. 6119-6123.

Research output: Contribution to journalArticle

Bortell, R. ; Owen, T. A. ; Bidwell, Joseph ; Gavazzo, P. ; Breen, E. ; Van Wijnen, A. J. ; Deluca, H. F. ; Stein, J. L. ; Lian, J. B. ; Stein, G. S. / Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 13. pp. 6119-6123.
@article{9bbf9d7f25b64e05b9eeb2edd2968e44,
title = "Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression",
abstract = "The observation that vitamin D-mediated enhancement of osteocalcin (OC) gene expression is dependent on and reciprocally related to the level of basal gene expression suggests that an interaction of the vitamin D responsive element (VDRE) with basal regulatory elements of the OC gene promoter contributes to both basal and vitamin D-enhanced transcription. Protein-DNA interactions at the VDRE of the rat OC gene (nucleotides -466 to -437) are reflected by direct sequence-specific and antibody-sensitive binding of the endogenous vitamin D receptor present in ROS 17/2.8 osteosarcoma nuclear protein extracts. In addition, a vitamin D-responsive increase in OC gene transcription is accompanied by enhanced non-vitamin D receptor-mediated protein-DNA interactions in the {"}TATA{"} box region (nucleotides -44 to +23), which also contains a potential glucocorticoid responsive element. Evidence for proximity of the VDRE with the basal regulatory elements is provided by two features of nuclear architecture. (i) Nuclear matrix attachment elements in the rat OC gene promoter that bind nuclear matrix proteins with sequence specificity may impose structural constraints on promoter conformation. (ii) Limited micrococcal nuclease digestion and Southern blot analysis indicate that three nucleosomes can be accommodated in the sequence spanning the OC gene VDRE, the OC/CCAAT box (nucleotides -99 to -76), and the TATA/glucocorticoid responsive element, and thereby the potential distance between the VDRE and the basal regulatory elements can be reduced. A model is presented for the contribution of both the VDRE and proximal promoter elements to the enhancement of OC gene transcription in response to vitamin D. The vitamin D receptor plus accessory proteins may function cooperatively with basal regulatory factors to modulate the extent to which the OC gene is transcribed.",
keywords = "Differentiation, Gene regulation, Hormone, Osteoblasts, Transcription",
author = "R. Bortell and Owen, {T. A.} and Joseph Bidwell and P. Gavazzo and E. Breen and {Van Wijnen}, {A. J.} and Deluca, {H. F.} and Stein, {J. L.} and Lian, {J. B.} and Stein, {G. S.}",
year = "1992",
month = "7",
day = "1",
language = "English (US)",
volume = "89",
pages = "6119--6123",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - Vitamin D-responsive protein-DNA interactions at multiple promoter regulatory elements that contribute to the level of rat osteocalcin gene expression

AU - Bortell, R.

AU - Owen, T. A.

AU - Bidwell, Joseph

AU - Gavazzo, P.

AU - Breen, E.

AU - Van Wijnen, A. J.

AU - Deluca, H. F.

AU - Stein, J. L.

AU - Lian, J. B.

AU - Stein, G. S.

PY - 1992/7/1

Y1 - 1992/7/1

N2 - The observation that vitamin D-mediated enhancement of osteocalcin (OC) gene expression is dependent on and reciprocally related to the level of basal gene expression suggests that an interaction of the vitamin D responsive element (VDRE) with basal regulatory elements of the OC gene promoter contributes to both basal and vitamin D-enhanced transcription. Protein-DNA interactions at the VDRE of the rat OC gene (nucleotides -466 to -437) are reflected by direct sequence-specific and antibody-sensitive binding of the endogenous vitamin D receptor present in ROS 17/2.8 osteosarcoma nuclear protein extracts. In addition, a vitamin D-responsive increase in OC gene transcription is accompanied by enhanced non-vitamin D receptor-mediated protein-DNA interactions in the "TATA" box region (nucleotides -44 to +23), which also contains a potential glucocorticoid responsive element. Evidence for proximity of the VDRE with the basal regulatory elements is provided by two features of nuclear architecture. (i) Nuclear matrix attachment elements in the rat OC gene promoter that bind nuclear matrix proteins with sequence specificity may impose structural constraints on promoter conformation. (ii) Limited micrococcal nuclease digestion and Southern blot analysis indicate that three nucleosomes can be accommodated in the sequence spanning the OC gene VDRE, the OC/CCAAT box (nucleotides -99 to -76), and the TATA/glucocorticoid responsive element, and thereby the potential distance between the VDRE and the basal regulatory elements can be reduced. A model is presented for the contribution of both the VDRE and proximal promoter elements to the enhancement of OC gene transcription in response to vitamin D. The vitamin D receptor plus accessory proteins may function cooperatively with basal regulatory factors to modulate the extent to which the OC gene is transcribed.

AB - The observation that vitamin D-mediated enhancement of osteocalcin (OC) gene expression is dependent on and reciprocally related to the level of basal gene expression suggests that an interaction of the vitamin D responsive element (VDRE) with basal regulatory elements of the OC gene promoter contributes to both basal and vitamin D-enhanced transcription. Protein-DNA interactions at the VDRE of the rat OC gene (nucleotides -466 to -437) are reflected by direct sequence-specific and antibody-sensitive binding of the endogenous vitamin D receptor present in ROS 17/2.8 osteosarcoma nuclear protein extracts. In addition, a vitamin D-responsive increase in OC gene transcription is accompanied by enhanced non-vitamin D receptor-mediated protein-DNA interactions in the "TATA" box region (nucleotides -44 to +23), which also contains a potential glucocorticoid responsive element. Evidence for proximity of the VDRE with the basal regulatory elements is provided by two features of nuclear architecture. (i) Nuclear matrix attachment elements in the rat OC gene promoter that bind nuclear matrix proteins with sequence specificity may impose structural constraints on promoter conformation. (ii) Limited micrococcal nuclease digestion and Southern blot analysis indicate that three nucleosomes can be accommodated in the sequence spanning the OC gene VDRE, the OC/CCAAT box (nucleotides -99 to -76), and the TATA/glucocorticoid responsive element, and thereby the potential distance between the VDRE and the basal regulatory elements can be reduced. A model is presented for the contribution of both the VDRE and proximal promoter elements to the enhancement of OC gene transcription in response to vitamin D. The vitamin D receptor plus accessory proteins may function cooperatively with basal regulatory factors to modulate the extent to which the OC gene is transcribed.

KW - Differentiation

KW - Gene regulation

KW - Hormone

KW - Osteoblasts

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=0026655337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026655337&partnerID=8YFLogxK

M3 - Article

C2 - 1321435

AN - SCOPUS:0026655337

VL - 89

SP - 6119

EP - 6123

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -