Osteocalcin gene promoter-binding factors are tissue-specific nuclear matrix components.
The nuclear matrix appears to play an important role in developmental gene expression during osteoblast differentiation. To better understand this role, we examined nuclear matrix DNA-binding proteins that are sequence-specific and interact with the osteocalcin gene promoter. Multiple protein-DNA interactions involving two distinct nuclear matrix proteins occur within the 5' regulatory sequences (nt -640 to -430). One of these proteins, NMP-1, is a ubiquitous, cell growth-regulated protein that is related to the transcription factor ATF and resides in both the nuclear matrix and the nonmatrix nuclear compartment. The other protein, NMP-2, is a cell type-specific, 38-kDa promoter factor that recognizes binding sites resembling the consensus site for the CCAAT/enhancer-binding protein C/EBP and is localized exclusively on the nuclear matrix. NMP-1 and NMP-2 each interact with two nuclear matrix protein-binding elements. These elements are present near key regulatory sites of the osteocalcin gene promoter, such as the principal steroid hormone (vitamin D)-responsive sequences. Binding in this region of the osteocalcin gene promoter suggests transient associations with the nuclear matrix that are distinct from the stable interactions of matrix attachment regions. Our results are consistent with involvement of the nuclear matrix in concentrating and/or localizing transcription factors that mediate the basal and steroid hormone responsiveness of osteocalcin gene transcription.
Bidwell
J P
JP
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655.
Van Wijnen
A J
AJ
Fey
E G
EG
Dworetzky
S
S
Penman
S
S
Stein
J L
JL
Lian
J B
JB
Stein
G S
GS
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D050981:Erythroid-Specific DNA-Binding Factors; D006657:Histones / Q000235:genetics; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015530:Nuclear Matrix / Q000378:metabolism*; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D015675:Osteocalcin / Q000235:genetics*; D012516:Osteosarcoma; D011401:Promoter Regions, Genetic; D051381:Rats; D013379:Substrate Specificity; D016385:TATA Box; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D006657:Histones; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D014157:Transcription Factors; C087950:nuclear matrix protein 2; D015675:Osteocalcin