1alpha,25-dihydroxy vitamin D(3) induces nuclear matrix association of the 1alpha,25-dihydroxy vitamin D(3) receptor in osteoblasts independently of its ability to bind DNA
Van Wijnen, Andre J.
Lian, Jane B.
van Zundert, Brigitte
Stein, Gary S.
Stein, Janet L.
Montecino, Martin A.
UMass Chan AffiliationsDepartment of Cell Biology
Cell Line, Tumor
Core Binding Factor Alpha 1 Subunit
Mediator Complex Subunit 1
Protein Structure, Tertiary
Recombinant Fusion Proteins
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Abstract1alpha,25-dihydroxy vitamin D(3) (vitamin D(3)) has an important role during osteoblast differentiation as it directly modulates the expression of key bone-related genes. Vitamin D(3) binds to the vitamin D(3) 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 D(3). 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 D(3) 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 D(3)-transcriptional upregulation.
SourceJ Cell Physiol. 2010 Feb;222(2):336-46. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/49579
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