Recruitment and subnuclear distribution of the regulatory machinery during 1alpha,25-dihydroxy vitamin D3-mediated transcriptional upregulation in osteoblasts
Department of Cell Biology
Medical Subject Headings
Active Transport, Cell Nucleus; Cell Nucleus; Cytoplasm; DNA; Humans; Ligands; Mediator Complex Subunit 1; Models, Biological; Osteoblasts; Protein Binding; Receptors, Calcitriol; Signal Transduction; *Transcription, Genetic; *Up-Regulation; Vitamin D
The architectural organization of the genome and regulatory proteins within the nucleus supports gene expression in a physiologically regulated manner. In osteoblastic cells ligand activation induces a nuclear punctate distribution of the 1alpha,25-dihydroxy vitamin D3 (1alpha,25(OH)2D3) receptor (VDR) and promotes its interaction with transcriptional coactivators such as SRC-1, NCoA-62/Skip, and DRIP205. Here, we discuss evidence demonstrating that in osteoblastic cells VDR binds to the nuclear matrix fraction in a 1alpha,25(OH)2D3-dependent manner. This interaction occurs rapidly after exposure to 1alpha,25(OH)2D3 and does not require a functional VDR DNA binding domain. The nuclear matrix-bound VDR molecules colocalize with the also nuclear matrix-associated coactivator DRIP205. We propose a model where the rapid association of VDR with the nuclear matrix fraction represents an event that follows 1alpha,25(OH)2D3-dependent nuclear localization of VDR, but that precedes 1alpha,25(OH)2D3-dependent transcriptional upregulation at target genes.
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Citation: J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):156-8. Epub 2010 Feb 18. Link to article on publisher's site