Sox9, a key transcription factor of bone morphogenetic protein-2-induced chondrogenesis, is activated through BMP pathway and a CCAAT box in the proximal promoter

2008 ◽  
Vol 217 (1) ◽  
pp. 228-241 ◽  
Author(s):  
Qiuhui Pan ◽  
Yongchun Yu ◽  
Qiongyu Chen ◽  
Chunsheng Li ◽  
Hong Wu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Proximal Promoter ◽  
Morphogenetic Protein ◽  
Bmp Pathway ◽  
Ccaat Box

scholarly journals Bone Morphogenetic Protein-2 (BMP-2) Activates NFATc1 Transcription Factor via an Autoregulatory Loop Involving Smad/Akt/Ca2+Signaling

2015 ◽  
Vol 291 (3) ◽  
pp. 1148-1161 ◽  
Author(s):  
Chandi C. Mandal ◽  
Falguni Das ◽  
Suthakar Ganapathy ◽  
Stephen E. Harris ◽  
Goutam Ghosh Choudhury ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

scholarly journals An osteogenesis-related transcription factor, core-binding factor A1, is constitutively expressed in the chondrocytic cell line TC6, and its expression is upregulated by bone morphogenetic protein-2

2000 ◽  
Vol 165 (3) ◽  
pp. 579-586 ◽  
Author(s):  
Y Takazawa ◽  
K Tsuji ◽  
A Nifuji ◽  
H Kurosawa ◽  
Y Ito ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Line ◽  
Bone Morphogenetic Protein ◽  
Blot Analysis ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Dependent Manner ◽  
Core Binding Factor ◽  
Morphogenetic Protein ◽  
Binding Factor

Core-binding factor A1 (Cbfa1), also called Pebp2 alpha A/AML3, is a transcription factor that belongs to the runt-domain gene family. Cbfa1-deficient mice are completely incapable of both endochondral and intramembranous bone formation, indicating that Cbfa1 is indispensable for osteogenesis. Maturation of chondrocytes in these mice is also disorganized, suggesting that Cbfa1 may also play a role in chondrogenesis. The aim of this study was to examine the expression and regulation of Pebp2 alpha A/AML3/Cbfa1 expression in the chondrocyte-like cell line, TC6. Northern blot analysis indicated that Cbfa1 mRNA was constitutively expressed as a 6.3 kb message in TC6 cells and the level of Cbfa1 expression was enhanced by treatment with bone morphogenetic protein-2 (BMP2) in a time- and dose-dependent manner. This effect was blocked by an RNA polymerase inhibitor, 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole, but not by a protein synthesis inhibitor, cycloheximide. Western blot analysis of the cell lysates using polyclonal antibody raised against Cbfa1 indicated that BMP2 treatment increased the Cbfa1 protein level in TC6 cells. In TC6 cells, BMP2 treatment enhanced expression of alkaline phosphatase and type I collagen mRNAs but suppressed that of type II collagen mRNA. In addition to TC6 cells, Cbfa1 mRNA was also expressed in primary cultures of chondrocytes and BMP2 treatment enhanced Cbfa1 mRNA expression in these cells similarly to its effect on TC6 cells. These data indicate that the Pebp2 alpha A/AML3/Cbfa1 gene is expressed in a chondrocyte-like cell line, TC6, and its expression is enhanced by treatment with BMP.

Bone morphogenetic protein-2 induces expression of murine zinc finger transcription factor ZNF450

2004 ◽  
Vol 94 (1) ◽  
pp. 202-215 ◽  
Author(s):  
Alasdair J. Edgar ◽  
Sharon L. Dover ◽  
Melanie N. Lodrick ◽  
Ian J. McKay ◽  
Francis J. Hughes ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Zinc Finger ◽  
Bone Morphogenetic Protein 2 ◽  
Zinc Finger Transcription Factor ◽  
Morphogenetic Protein

scholarly journals Cloning and functional characterization of the 5′-flanking region of the human bone morphogenetic protein-2 gene

1999 ◽  
Vol 338 (2) ◽  
pp. 433-440 ◽  
Author(s):  
Takeyuki SUGIURA
Keyword(s):  
Bone Morphogenetic Protein ◽  
Promoter Region ◽  
Transforming Growth Factor ◽  
Functional Characterization ◽  
Bone Morphogenetic Protein 2 ◽  
Proximal Promoter ◽  
Phage Library ◽  
Promoter Regions ◽  
Morphogenetic Protein ◽  
Flanking Region

Bone morphogenetic protein-2 (BMP-2) is involved in bone formation, organogenesis or pattern formation during development. The expression of BMP-2 is regulated accurately and coordinately with that of other transforming growth factor-β (TGF-β) superfamily members. To elucidate the mechanism underlying the regulation of BMP-2 expression, a 6.7 kb SpeI–SalI fragment, from the P1 phage library, encompassing the 5´-flanking region of the human BMP-2 gene, was isolated and sequenced. Transcription start sites were mapped by the 5´-rapid amplification of cDNA ends (RACE) method. It has been found that the human BMP-2 gene contains, largely, two promoter regions surrounded by GC-rich sequences with several Sp1 consensus motifs. The proximal promoter possesses a single start site, whereas several start sites are clustered in the distal promoter region. Neither TATA nor CAAT consensus sequences are found in the proximity of the start sites for either promoter. Interestingly, in no case is the transcription-initiation site common between the human and mouse BMP-2 genes, although the sequence of the BMP-2 gene is well conserved in the promoter region between two species. Transient transfection experiments with the reporter fused with various lengths of the BMP-2 promoter sequence demonstrated that there exist enhancer elements in an 1.1 kb GC-rich fragment covering both promoter regions. It is noteworthy that the enhancer elements are 5´-flanked by a 790 bp strong repressor element that is characterized by numerous AT stretches. This intriguing organization may be amenable to the tight control of the expression of BMP-2 that is essential for development or bone morphogenesis.

scholarly journals The Zinc Finger Transcription Factor Gli2 Mediates Bone Morphogenetic Protein 2 Expression in Osteoblasts in Response to Hedgehog Signaling

2006 ◽  
Vol 26 (16) ◽  
pp. 6197-6208 ◽  
Author(s):  
Ming Zhao ◽  
Mei Qiao ◽  
Stephen E. Harris ◽  
Di Chen ◽  
Babatunde O. Oyajobi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Hedgehog Signaling ◽  
Osteoblast Differentiation ◽  
Promoter Activity ◽  
Bone Morphogenetic Protein 2 ◽  
Dependent Manner ◽  
Genetic Ablation ◽  
Morphogenetic Protein

ABSTRACTBone morphogenetic protein 2 (BMP-2) plays a critical role in osteoblast function. InDrosophila, Cubitus interruptus (Ci), which mediates hedgehog signaling, regulates gene expression ofdpp, the ortholog of mammalian BMP-2. Null mutation of the transcription factor Gli2, a mammalian homolog of Ci, results in severe skeletal abnormalities in mice. We hypothesize that Gli2 regulates BMP-2 gene transcription and thus osteoblast differentiation. In the present study, we show that overexpression of Gli2 enhances BMP-2 promoter activity and mRNA expression in osteoblast precursor cells. In contrast, knocking down Gli2 expression by Gli2 small interfering RNA or genetic ablation of the Gli2 gene results in significant inhibition of BMP-2 gene expression in osteoblasts. Promoter analyses, including chromatin immunoprecipitation and electrophoretic mobility shift assays, provided direct evidence that Gli2 physically interacts with the BMP-2 promoter. Functional studies showed that Gli2 is required for osteoblast maturation in a BMP-2-dependent manner. Finally, Sonic hedgehog (Shh) stimulates BMP-2 promoter activity and osteoblast differentiation, and the effects of Shh are mediated by Gli2. Taken together, these results indicate that Gli2 mediates hedgehog signaling in osteoblasts and is a powerful activator of BMP-2 gene expression, which is required in turn for normal osteoblast differentiation.

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