Initiator Elements Function to Determine the Activity State of BX-C Enhancers

Initiator Elements Function to Determine the Activity State of BX-C Enhancers: "Author Summary

Understanding how genes become activated is one of the primary areas of research in modern biology. In order to decipher the DNA components required for this process, scientists have traditionally turned to transgenic reporter assays, where DNA elements are removed from their native environment and placed next to a simplified reporter gene to monitor transcriptional activation. Although this approach is powerful, it can result in artifacts stemming from the channelization of regulatory element activities into predetermined classes. In this manuscript, we investigate the biological role of elements from the Drosophila bithorax complex, called initiators. In transgenic assays, these elements have been categorized as enhancers. However, genetic analysis suggests that, in situ, these elements perform a far more complex function. Here, using a new method to repeatedly target a genetic locus for mutagenesis, we show that initiators function as control elements that coordinate the activity of nearby enhancers and silencers. Overall, our study highlights how gene expression can be controlled through a hierarchical arrangement of cis-regulatory elements.

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