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. One mechanism whereby transcription factor activities are modulated is through direct interactions with cofactors. In addition, 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.
The Twist transcription factor represents an ideal model for studying the regulation of transcription factor activity throughout development. Twist is a highly conserved transcription factor that is a key regulator of many developmental programs during embryogenesis as well as cancer metastasis 
. In Drosophila melanogaster
, Twist regulates multiple, discrete steps of mesoderm development, including gastrulation, segregation of populations of mesodermal cells, establishment and formation of the somatic musculature, and finally establishment of the adult musculature 
. To achieve these diverse activities, Twist regulates a large number of target genes temporally within a discrete lineage resulting in a diverse array of outputs during mesodermal development 
. A key question is how these diverse outputs of Twist activity during development are achieved.
The varied roles of Twist during different phases of embryonic development and the large number of Twist-regulated target genes suggest complex regulation of Twist activity 
. Twist activity is often modulated by interactions with other transcription factors 
. Twist is a basic Helix-loop-Helix (bHLH) transcription factor that can homodimerize or heterodimerize, with distinct activities for each dimer pair. For example, Twist homodimers are responsible for activating target genes that direct cells to the somatic myogenic lineage 
. By contrast, heterodimers between Twist and another bHLH protein, Daughterless, repress the somatic myogenic lineage 
. Twist activity is also regulated by interactions with other transcription regulators that bind closely linked DNA regulatory elements. One such interaction, with the NF-κB orthologue Dorsal, produces synergistic rather than cooperative activation of Dorsal targets during development 
. Hence, Daughterless and Dorsal are examples of transcription regulators that physically interact with Twist to modify its output.
Other mechanisms that regulate Twist activity during development are less clear. One mechanism whereby transcriptional activity is indirectly regulated is through the action of chromatin modifying factors that generate a local chromatin environment that allows and/or favors the expression of a specific target gene. The structure of chromatin is modified by two predominant mechanisms: the marking of nucleosome tails with post-translational modifications such as acetylation, phosphorylation and methylation, and the remodeling of the local chromatin environment via factors that reposition nucleosomes in a local gene environment 
. Nucleosome repositioning occurs via the activity of ATP-dependent chromatin remodeling complexes such as the Brahma-containing (BRM) complex, the Drosophila
orthologue of the yeast SWI/SNF chromatin remodeling complex 
. Mutations in BRM complex subunits have revealed essential roles for BRM in such processes as homeotic gene expression, oogenesis, and cell cycle control 
. Loss-of-function studies have determined that BRM-regulated chromatin remodeling activity is required for most RNA Polymerase II-regulated transcription 
. Most eukaryotic organisms have two different compositions of the SWI/SNF complex; in Drosophila
, these complexes are designated the BAP (Osa-containing) and PBAP (polybromo/Bap180, Bap170 and SAYP-containing) complexes 
. Both BAP and PBAP are linked to gene activation and repression, are present in the same cells, and perform unique yet cooperative functions during development 
. Both the association of BRM complexes with transcription factors and BRM complex targeting and regulation during embryogenesis remain an area of considerable interest. Moreover, links between BRM complexes, chromatin remodeling and Twist have not yet been elucidated.
The nuclear protein Akirin was shown to regulate gene expression in several different transcription pathways, yet its mechanism of action remained unclear 
. Here we identify Akirin as a factor that facilitates an interaction between Twist and the BRM chromatin remodeling complex to promote gene expression. We find that Akirin interacts both physically and genetically with Twist at Twist-dependent enhancer regions and positively regulates expression of Dmef2
, a Twist-regulated gene that is critical for somatic myogenesis during development. As would be predicted by this interaction, akirin
mutant embryos show a range of somatic muscle phenotypes. Akirin is widely associated with regions of active transcription. We find that Akirin colocalizes with subunits of the BRM chromatin remodeling complex on polytene chromosomes and interacts genetically with core subunits of the BRM complex during myogenesis. Finally, we verify with chromatin immunoprecipitation that Twist, Akirin, and a core subunit of the BRM complex all occupy the Twist-dependent Dmef2
enhancer. Curiously, Akirin/Twist interactions are not required at all Twist-dependent enhancers, as evidenced by our chromatin immunoprecipitation experiments at the eve
MHE. These results suggest that Akirin functions as a BRM accessory protein that links the BRM chromatin remodeling machinery to Twist transcription factor activity at a subset of Twist-regulated enhancers. These results provide a common mechanism by which Akirin links chromatin remodeling factors to spatiotemporal-specific gene activation.