title: Recruitment and subnuclear distribution of the regulatory machinery during 1alpha,25-dihydroxy vitamin D3-mediated transcriptional upregulation in osteoblasts.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Concepcion, Worcester, MA, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Arriagada
authors.forename: Berta
authors.initials: B
authors.lastname: Henriquez
authors.forename: Daniel
authors.initials: D
authors.lastname: Moena
authors.forename: Paola
authors.initials: P
authors.lastname: Merino
authors.forename: Cinthya
authors.initials: C
authors.lastname: Ruiz-Tagle
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Martin
authors.initials: M
authors.lastname: Montecino
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D008024:Ligands; D056913:Mediator Complex Subunit 1 / Q000737:chemistry; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism*; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008024:Ligands; D056913:Mediator Complex Subunit 1; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D004247:DNA