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.
Highlights
A fundamental question in embryonic development is how diverse cell lineages are specified, patterned and organized from a single common progenitor
We examined the activity of the evolutionarily conserved transcription factor Twist during embryogenesis of Drosophila melanogaster
Akirin is required for optimal expression of a Twistdependent target during muscle development via interactions with the Drosophila SWI/SNF chromatin remodeling complex
Summary
A fundamental question in embryonic development is how diverse cell lineages are specified, patterned and organized from a single common progenitor These processes are governed by distinct gene expression programs administered by tightly regulated transcription factor activities during embryonic development. Links between transcription factors and the general transcription machinery can be indirect, such as the actions of secondary factors that recruit chromatin remodeling complexes to modify the local chromatin environment and allow gene activation. The identification of these secondary effectors and their in vivo function is critical for understanding the regulation of transcription factor activity during embryonic development. Such interactions have significant ramifications for developmental disorders and diseases such as cancer
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