The osteocalcin gene promoter provides a molecular blueprint for regulatory mechanisms controlling bone tissue formation: role of transcription factors involved in development.
Characterization of regulatory sequences and their cognate binding factors in the bone-specific osteocalcin (OC) gene promoter has provided insight into mechanisms that control expression of the gene under diverse biological conditions. We present evidence for AP-1 motifs and two multipartite conserved regulatory sequences, the OC Box I (nt-99 to-76) and a site designated OC Box II (nt-136 to-130) in contributing to developmental and tissue-specific expression of osteocalcin. OC Box I is characterized by a homeodomain binding site and OC Box II is a recognition sequence for AML-1 (also called PEBP2 alpha), a runt homology-related DNA binding protein. Functional activity of the elements was established in osseous and non-osseous cell lines and is in part related to the binding of osteoblast-specific complexes which enhance OC transcription. The contribution of several elements and binding of multiple classes of transcription factors to independent elements in both these domains serve to illustrate the complexity of control required for tissue-specific OC expression.
Lian
J B
JB
University of Massachusetts Medical Center, Department of Cell Biology, Worcester 01655, USA.
Stein
G S
GS
Stein
J L
JL
Van Wijnen
A
A
McCabe
L
L
Banerjee
C
C
Hoffmann
H
H
D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000166:cytology; D002454:Cell Differentiation; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018398:Homeodomain Proteins / Q000378:metabolism; D051957:MSX1 Transcription Factor; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; C497998:Msx1 protein, rat; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D015675:Osteocalcin