1α,25-dihydroxy vitamin D3 induces nuclear matrix association of the 1α,25-dihydroxy vitamin D3 receptor in osteoblasts independently of its ability to bind DNA

Gloria Arriagada, Roberto Paredes, Andre J. Van Wijnen, Jane B. Lian, Brigitte Van Zundert, Gary S. Stein, Janet L. Stein, Martin Montecino

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

1α,25-dihydroxy vitamin D3 (vitamin D3) has an important role during osteoblast differentiation as it directly modulates the expression of key bone-related genes. Vitamin D3 binds to the vitamin D3 receptor (VDR), a member of the superfamily of nuclear receptors, which in turn interacts with transcriptional activators to target this regulatory complex to specific sequence elements within gene promoters. Increasing evidence demonstrates that the architectural organization of the genome and regulatory proteins within the eukaryotic nucleus support gene expression in a physiological manner. Previous reports indicated that the VDR exhibits a punctate nuclear distribution that is significantly enhanced in cells grown in the presence of vitamin D3. Here, we demonstrate that in osteoblastic cells, the VDR binds to the nuclear matrix in a vitamin D 3-dependent manner. This interaction of VDR with the nuclear matrix occurs rapidly after vitamin D3 addition and does not require a functional VDR DNA-binding domain. Importantly, nuclear matrix-bound VDR colocalizes with its transcriptional coactivator DRIP205/TRAP220/MED1 which is also matrix bound. Together these results indicate that after ligand stimulation the VDR rapidly enters the nucleus and associates with the nuclear matrix preceding vitamin D3-transcriptional upregulation.

Original languageEnglish (US)
Pages (from-to)336-346
Number of pages11
JournalJournal of Cellular Physiology
Volume222
Issue number2
DOIs
StatePublished - Feb 2010

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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