Reference - Detail
|Author||Katagiri T, Imada M, Yanai T, Suda T, Takahashi N, Kamijo R.|
|Title||Identification of a BMP-responsive element in Id1, the gene for inhibition of myogenesis.|
BACKGROUND:Bone morphogenetic protein-2 (BMP-2) stimulates osteoblast differentiation, but inhibits myogenic differentiation in C2C12 myoblasts. BMP-2 induces transcription of Id1, an inhibitor for myogenesis, within 1 h in the cells. To examine the molecular mechanism of the action of BMP-2, we analysed a BMP-2-responsive element (BRE) in the 5' flanking region of the human Id1 gene.
RESULTS:A GC-rich region between -985 bp and -957 bp of the human Id1 gene was identified as a BRE. The BRE containing promoter activity was stimulated by BMP-2 or by constitutively active BMP receptors (BMPR-IA and BMPR-IB). The stimulation was blocked by co-transfecting with dominant negative BMPR-IA or Smad7. A unique DNA-protein complex was induced in response to BMP-2 on the BRE. The complex induced by BMP-2 contained Smad1 and Smad4, possibly as a complex of both Smads. BMP-2 failed to stimulate the expression of Id1 mRNA in Smad4-deficient cells. Over-expression of Smad4, but not Smad1, stimulated the Id1 reporter activity and the expression of endogenous Id1 mRNA in Smad4-deficient cells.
CONCLUSION:Signalling of BMP-2 to stimulate the expression of Id1 would be transduced by BMPR-IA and mediated by Smad1 and Smad4, both of which form a complex on the 29 bp GC-rich element.
|MeSH||Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Protein Receptors, Type I Bone Morphogenetic Proteins / metabolism* Cell Line DNA-Binding Proteins / metabolism Enzyme Inhibitors / metabolism Genes, Reporter Helix-Loop-Helix Motifs Humans Inhibitor of Differentiation Protein 1 Mice Mitogen-Activated Protein Kinases / antagonists & inhibitors Phosphoinositide-3 Kinase Inhibitors Promoter Regions, Genetic Protein Binding Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Receptors, Growth Factor / genetics Receptors, Growth Factor / metabolism Repressor Proteins* Response Elements / genetics* Signal Transduction / physiology* Smad Proteins Smad1 Protein Smad4 Protein Trans-Activators / metabolism Transcription Factors / genetics* Transcription Factors / metabolism Transforming Growth Factor beta*|
|WOS Category||GENETICS & HEREDITY CELL BIOLOGY|
|Human and Animal Cells|