Subnuclear distribution of the vitamin D receptor.
The subnuclear distribution of the vitamin D receptor was investigated to begin addressing the contribution of nuclear architecture to vitamin D-responsive control of gene expression in ROS 17/2.8 rat osteosarcoma cells. The nuclear matrix is an anastomosing network of filaments that is functionally associated with DNA replication, transcription, and RNA processing. The representation of vitamin D receptor in the nuclear matrix and nonmatrix nuclear fractions was determined by the combined application of 1) sequence-specific interactions with the vitamin D receptor binding element of the rat bone-specific osteocalcin gene promoter and 2) Western blot analysis. Both methods confirmed the presence of vitamin D receptor in the nonmatrix nuclear fraction and the absence of detectable vitamin D receptors associated with the nuclear matrix. In contrast, these same nuclear matrix proteins preparations exhibited association with the general transcription factor AP-1 and a bone tissue-specific promoter binding factor NMP2. NMP-2 exhibits recognition for a promoter domain contiguous to the vitamin D-responsive element of the osteocalcin gene, although the vitamin D receptor does not appear to be a component of the nuclear matrix proteins. Interrelationships between nuclear matrix proteins and nonmatrix nuclear proteins, in mediating steroid hormone responsiveness of a vitamin D-regulated promoter, are therefore suggested.
Department of Cell Biology, University of Massachusetts, Worcester 01655.
J P
JP
Bidwell
A J
AJ
van Wijnen
E G
EG
Fey
H
H
Merriman
S
S
Penman
J L
JL
Stein
G S
GS
Stein
J B
JB
Lian
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D008969:Molecular Sequence Data; D015530:Nuclear Matrix / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012516:Osteosarcoma; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol / Q000032:analysis* / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000494:pharmacology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D018167:Receptors, Calcitriol; D014157:Transcription Factors; C087950:nuclear matrix protein 2; D014807:Vitamin D; D004247:DNA