A view through a chromatin loop: insights into the ecdysone activation of early genes in Drosophila

The early genes are a key group of ecdysone targets that function at the top of the signaling hierarchy. In the presence of ecdysone, early genes exhibit a highly characteristic rapid and powerful induction that represents a primary response. Multiple isoforms encoded by early genes then coordinate the activation of a larger group of late genes. While the general mechanism of ecdysone-dependent transcription is well characterized, it is not known whether a distinct mechanism governs the hormonal response of early genes. We previously found that one of the Drosophila early genes, E75, harbors multiple functional ecdysone response elements (EcREs). In this study we extended the analysis to Broad and E74 and found that EcRE multiplicity is a general feature of the early genes. Since most of the EcREs within early gene loci are situated distantly from promoters, we employed the chromosome conformation capture method to determine whether higher order chromatin structure facilitates hormonal activation. For each early gene we detected chromatin loops that juxtapose their promoters and multiple distant EcREs prior to ecdysone activation. Our findings suggest that higher order chromatin structure may serve as an important mechanism underlying the distinct response of early genes to ecdysone.