Mechanisms of transcriptional regulation by Runt domain proteins

Runt domain proteins have vital roles in regulating transcription in develo pmental pathways extending-from sex determination and segmentation in fruit fly embryos to the development of blood and bone in mammals. Many of the i nsights into the mechanisms by which these proteins act to regulate transcr iption originate either from studies on the Drosophila runt gene, the found ing member of this family, or from work on the mammalian PEBP2/CBF transcri ption factor. Genetic experiments in the Drosophila system reveal that runt functions both to activate and to repress transcription of different downs tream target genes and indicate that different mechanisms are used in the r egulation of differ ent specific downstream target genes. These studies hav e also identified other nuclear factors that work with Runt in some of thes e pathways. Studies in mammalian systems have provided additional evidence for the complexity of transcriptional regulation by Runt domain proteins an d have identified other transcription factors that cooperate with Runt doma in proteins to regulate the activity of different specific cis-regulatory e nhancers. The emerging view from studies in both systems is that these prot eins act as context-dependent regulators of transcription, activating or re pressing gene expression dependent upon the constitution of a particular pr omoter/enhancer in a particular cell type. These results have yielded neu i nsights into the molecular mechanisms that control animal development and p rovide a framework for investigating fundamental issues in eukaryotic trans criptional regulation.