Akirin: a novel link between Twist transcription factor activity and Brahma chromatin remodeling complexes during embryogenesis. Scott J. Nowak1, Hitoshi Aihara3, Katie Gonzalez2, Yutaka Nibu3, Mary K. Baylies2. 1) Dept. of Biology and Physics, Kennesaw State University, Kennesaw, GA 30144; 2) Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065; 3) Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065.
The activities of developmentally critical transcription factors are regulated via interactions with accessory proteins that confer both tissue and target specificity for transcription factor activity. We identified Akirin, a highly conserved nuclear protein, as a novel cofactor of the key Drosophila mesoderm and muscle transcriptional regulator, Twist. Like twist hypomorphic mutants, akirin mutant embryos have misattached or missing muscles and severely altered muscle morphology. Akirin interacts with Twist to facilitate expression of some, but not all, Twist-regulated genes during embryonic myogenesis. To regulate transcription, Akirin colocalizes and genetically interacts with subunits of the Brahma SWI/SNF-class chromatin remodeling complex at Twist-target genes. This suggests that Akirin mediates a novel link between Twist and chromatin remodeling complexes to facilitate Twist-regulated transcription during Drosophila myogenesis. These results also provide a common mechanism by which Akirin, through further interactions with chromatin remodeling factors, regulates the activities of multiple transcription factors during development, the immune response and homeostasis.