The abdominal-B promoter tethering element mediates promoter-enhancer specificity at the Drosophila bithorax complex

At the Drosophila bithorax complex many distinct classes of cis-regulatory modules work collectively during development to control gene expression. Abdominal-B (Abd-B) is one of three homeotic genes in the BX-C and is expressed in specific presumptive abdominal segments in the embryo. The transcription of Abd-B is tightly controlled by an array of cis-regulatory modules that direct its expression over extended genomic distances. These regulatory modules include promoters, insulators, silencers, enhancers, promoter targeting sequences and the recently identified promoter tethering element (PTE). To activate gene expression at the endogenous complex, enhancers located >50 kb away must bypass intervening insulators to interact with the Abd-B promoter. The molecular mechanisms that allow enhancers to bypass insulators are not currently well understood. In this short article, we report on a novel mechanism for insulator bypass involving the PTE. In addition, we use bioinformatic analysis across twelve Drosophila genomes to identify putative cis-regulatory sequences that may be capable of facilitating specific promoter-enhancer interactions at the bithorax complex and propose a model for their molecular function during development.