CBFa(AML/PEBP2)-related elements in the TGF-beta type I receptor promoter and expression with osteoblast differentiation.
Organization of the transforming growth factor-beta (TGF-beta) type I receptor (TRI) promoter predicts constitutive transcription, although its activity increases with differentiation status in cultured osteoblasts. Several sequences in the rat TRI promoter comprise cis-acting elements for CBFa (AML/PEBP2alpha) transcription factors. By gel mobility shift and immunological analyses, a principal osteoblast-derived nuclear factor that binds to these sites is CBFa1 (AML-3/PEBP2alphaA). Rat CBFa1 levels parallel expression of the osteoblast phenotype and increase under conditions that promote mineralized bone nodule formation in vitro. Fusion of CBFa binding sequence from the TRI promoter to enhancer-free transfection vector increases reporter gene expression in cells that possess abundant CBFa1, and overexpression of CBFa increase the activity of transfected native TRI promoter/reporter plasmid. Consequently, phenotype-restricted use of cis-acting elements for CBFa transcription factors can contribute to the high levels of TRI that parallel osteoblast differentiation and to the potent effects of TGF-beta on osteoblast function.
Ji
C
C
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA.
Casinghino
S
S
Chang
D J
DJ
Chen
Y
Y
Javed
A
A
Ito
Y
Y
Hiebert
S W
SW
Lian
J B
JB
Stein
G S
GS
McCarthy
T L
TL
Centrella
M
M
D030201:Activin Receptors, Type I; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat