Specific combinations of boundary element and Polycomb response element are required for the regulation of the Hox genes in Drosophila melanogaster

In the bithorax complex of Drosophila melanogaster, the chromatin boundary elements (BE) demarcate cis-regulatory domains that regulate Hox genes along the anteroposterior body axis. These elements are closely associated with the Polycomb Response Elements (PREs) and restrict the ectopic activation of cis-regulatory domains during development. The relevance of such specific genomic arrangements of regulatory elements remains unclear. Deletions of individual BE-PRE combination result in distinct homeotic phenotypes. In this study, we show that deletion of two such BE-PRE combinations in cis leads to new genetic interactions, which manifests as dorsal closure defect phenotype in adult abdominal epithelia. We further demonstrate that dorsal closure phenotype results from enhanced and ectopic expression of Hox gene Abd-B in the larval epithelial cells. This suggests a specific role of multiple BE-PRE combinations in the larval epithelial cells for regulation of Abd-B. Using chromosome conformation capture experiments, we show that genetic interactions correlate with direct physical interactions among the BE-PRE combinations. Our results demonstrate the functional relevance of the closely associated BE and PRE combinations in regulation of Hox genes.