Redundant function of Runt Domain binding partners, Big brother and Brother, during Drosophila development

The Core Binding Factor is a heterodimeric transcription factor complex in vertebrates that is composed of a DNA binding alpha -subunit and a non-DNA binding beta -subunit. The alpha -subunit is encoded by members of the Runt Domain family of proteins and the beta -subunit is encoded by the CBF gene . In Drosophila, two genes encoding alpha -subunits, runt and lozenge, and two genes encoding beta -subunits, Big brother and Brother, have been previ ously identified. Here, a sensitized genetic screen was used to isolate mut ant alleles of the Big brother gene. Expression studies show that Big broth er is a nuclear protein that co-localizes with both Lozenge and Runt in the eye imaginal disc. The nuclear localization and stability of Big brother p rotein is mediated through the formation of heterodimeric complexes between Big brother and either Lozenge or Runt. Big brother functions with Lozenge during cell fate specification in the eye, and is also required for the de velopment of the embryonic PNS. ds-RNA-mediated genetic interference experi ments show that Brother and Big brother are redundant and function together with Runt during segmentation of the embryo. These studies highlight a mec hanism for transcriptional control by a Runt Domain protein and a redundant pair of partners in the specification of cell fate during development.