Wnt信号通路
增强子
运行x2
骨形态发生蛋白
转录因子
生物
细胞生物学
基因
SMAD公司
发起人
骨形态发生蛋白2
遗传学
基因表达
体外
作者
Eddie Rodríguez-Carballo,Arnau Ulsamer,Antonio R.G. Susperregui,María Cristina Manzanares Céspedes,Eva Sánchez-García,Ramón Bartrons,José Luís Rosa,Francesc Ventura
摘要
Abstract Osteoblast differentiation depends on the coordinated network of evolutionary conserved transcription factors during bone formation and homeostasis. Evidence indicates that bone morphogenetic protein (BMP) and Wnt proteins regulate several steps of skeletal development. Here, we provide a molecular description of the cooperative effects of BMP and Wnt canonical pathway on the expression of the early osteogenic genes Dlx5, Msx2, and Runx2 in C2C12 cells, primary cultures of bone marrow–mesenchymal stem cells, and organotypic calvarial cultures. Coordinated regulation of these genes leads to the cooperative activation of their downstream osteogenic target gene osterix. Induction of these genes is mediated through enhancer regions with an evolutionary conserved structure encompassing both Smad and TCF/LEF1 DNA-binding sites. Formation of a cooperative complex is mediated through DNA binding of Smads and TCF4/β-catenin to their cognate sequences, as well as protein-protein interactions between them. The formation of these cooperative transcriptional complexes results in a more efficient recruitment of coactivators such as p300. We propose that evolutionary conserved regulatory regions in specific osteogenic master genes are key integrative modules during osteogenesis. © 2011 American Society for Bone and Mineral Research.
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