GAGA-associated factor fosters loop formation in the Drosophila genome

The impact of genome organization on the control of gene expression persists as a major challenge in reg-ulatory biology. Most efforts have focused on the role of CTCF-enriched boundary elements and TADs, which enable long-range DNA-DNA associations via loop extrusion processes. However, there is increasing evi-dence for long-range chromatin loops between promoters and distal enhancers formed through specific DNA sequences, including tethering elements, which bind the GAGA-associated factor (GAF). Previous studies showed that GAF possesses amyloid properties in vitro, bridging separate DNA molecules. In this study, we investigated whether GAF functions as a looping factor in Drosophila development. We employed Micro-C assays to examine the impact of defined GAF mutants on genome topology. These studies suggest that the N-terminal POZ/BTB oligomerization domain is important for long-range associations of distant GAGA-rich tethering elements, particularly those responsible for promoter-promoter interactions that coor-dinate the activities of distant paralogous genes.

Automated summary

The impact of genome organization on gene expression control is a major challenge in regulatory biology. Previous research has focused on CTCF-enriched boundary elements and TADs, which enable long-range DNA associations. However, there is increasing evidence for long-range chromatin loops between promoters and enhancers formed through specific DNA sequences, including tethering elements that bind the GAGA-associated factor (GAF). This study investigates the role of GAF as a looping factor in Drosophila development and finds that the N-terminal POZ/BTB oligomerization domain is crucial for the associations of distant tethering elements responsible for coordinating the activities of distant paralogous genes.