title: Akirin links twist-regulated transcription with the Brahma chromatin remodeling complex during embryogenesis.
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.
authors.affiliation: Program in Developmental Biology, Sloan Kettering Institute, New York, New York, United States of America.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Nowak
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aihara
authors.forename: Katie
authors.initials: K
authors.lastname: Gonzalez
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nibu
authors.forename: Mary K
authors.initials: MK
authors.lastname: Baylies
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D047108:Embryonic Development; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D009132:Muscles / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000235:genetics; D009687:Nuclear Proteins; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C526726:akirin protein, Drosophila; C086469:brm protein, Drosophila