Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene

Jane B. Lian, Janet L. Stein, Gary S. Stein, Martin Montecino, André J. Van Wijnen, Amjad Javed, Soraya Gutierrez

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The vitamin D response element in the bone tissue-specific osteocalcin gene has served as a prototype for understanding molecular mechanisms regulating physiologic responsiveness of vitamin D-dependent genes in bone cells. We briefly review factors which contribute to vitamin D transcriptional control. The organization of the vitamin D response element (VDRE), the multiple activities of the vitamin D receptor transactivation complex, and the necessity for protein-protein interactions between the VDR-RXR heterodimer activation complex and DNA binding proteins at other regulatory elements, including AP-1 sites and TATA boxes, provide for precise regulation of gene activity in concert with basal levels of transcription. We present evidence for molecular mechanisms regulating vitamin D-dependent mediated transcription of the osteocalcin gene that involve chromatin structure of the gene and nuclear architecture. Modifications in nucleosomal organization, DNase I hypersensitivity and localization of vitamin D receptor interacting proteins in subnuclear domains are regulatory components of vitamin D-dependent gene transcription. A model is proposed to account for the inability of vitamin D induction of the osteocalcin gene in the absence of ongoing basal transcription by competition of the YY1 nuclear matrix-associated transcription factor for TFIIB-VDR interactions. Activation of the VDR-RXR complex at the OC VDRE occurs through modifications in chromatin mediated in part by interaction of OC gene regulatory sequences with the nuclear matrix-associated Cbfa1 (Runx2) transcription factor which is required for osteogenesis.

Original languageEnglish
Pages (from-to)159-170
Number of pages12
JournalSteroids
Volume66
Issue number3-5
DOIs
Publication statusPublished - 1 May 2001

Keywords

  • Cbfa1
  • Chromatin
  • Nuclear matrix
  • Osteocalcin
  • Transcription
  • Vitamin D steroid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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