Recruitment and subnuclear distribution of the regulatory machinery during 1alpha,25-dihydroxy vitamin D3-mediated transcriptional upregulation in osteoblasts.
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.
Arriagada
Gloria
G
Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Concepcion, Worcester, MA, USA.
Henriquez
Berta
B
Moena
Daniel
D
Merino
Paola
P
Ruiz-Tagle
Cinthya
C
Lian
Jane B
JB
Stein
Gary S
GS
Stein
Janet L
JL
Montecino
Martin
M
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
D008024:Ligands; D056913:Mediator Complex Subunit 1; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D004247:DNA