Abstract: |
The activities of developmentally critical transcription factors are regulated via interactions with cofactors. Such interactions influence transcription factor activity either directly through protein-protein interactions or indirectly by altering the local chromatin environment. Using a yeast double-interaction screen, we identified a highly conserved nuclear protein, Akirin, as a novel cofactor of the key Drosophila melanogaster mesoderm and muscle transcription factor Twist. We find that Akirin interacts genetically and physically with Twist to facilitate expression of some, but not all, Twist-regulated genes during embryonic myogenesis. akirin mutant embryos have muscle defects consistent with altered regulation of a subset of Twist-regulated genes. To regulate transcription, Akirin colocalizes and genetically interacts with subunits of the Brahma SWI/SNF-class chromatin remodeling complex. Our results suggest that, mechanistically, Akirin mediates a novel connection between Twist and a chromatin remodeling complex to facilitate changes in the chromatin environment, leading to the optimal expression of some Twist-regulated genes during Drosophila myogenesis. We propose that this Akirin-mediated link between transcription factors and the Brahma complex represents a novel paradigm for providing tissue and target specificity for transcription factor interactions with the chromatin remodeling machinery. © 2012 Nowak et al. |
Keywords: |
protein expression; unclassified drug; genetics; mutation; nonhuman; protein localization; protein analysis; cell cycle protein; nonhistone protein; phenotype; animal; metabolism; animals; cell cycle proteins; chromosomal proteins, non-histone; animal tissue; nuclear protein; embryo; protein protein interaction; transcription factor; embryo development; transcription factors; gene expression regulation; prenatal development; gene expression regulation, developmental; transcription regulation; transactivator protein; muscle disease; trans-activators; drosophila melanogaster; transcription factor twist; mesoderm; drosophila proteins; embryonic development; chromatin assembly and disassembly; drosophila protein; muscle; muscles; muscle development; enhancer region; enhancer elements, genetic; myogenic factor; congenital malformation; twist transcription factor; brm protein; akirin1 protein, drosophila; brm protein, drosophila; mef2 protein, drosophila; swi snf b chromatin remodeling complex; swi-snf-b chromatin-remodeling complex; twi protein, drosophila; akirin; myogenic regulatory factors
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