The runt domain identifies a new family of heterometric transcriptional regulators

As is the case for every cell differentiation process, differentiation of a mesenchymal pluripotent cell into any cell type is governed in large part by transcription factors that trigger the entire program of cell differentiation. Our knowledge about the transcriptional control of osteoblast differentiation made its main strides at the end of the 20th century and has been significantly refined since then, with the emergence of novel mechanisms regulating gene expression in addition to transcription factors. Briefly and ideally, a transcription factor that is a differentiation factor for a given cell type should (1) be expressed in progenitors of this cell type, (2) regulate the expression of all cell-specific genes in this cell type, (3) induce expression of the aforementioned genes when ectopically expressed in other cell types (sufficiency criterion), and (4) be necessary for the differentiation of this cell type in vivo, in mice, and at best in humans. As presented in this chapter, the transcription factor currently viewed as the master gene of osteoblast differentiation is one of the very few differentiation factors to fulfill all these criteria.