What are tethering elements?

High-resolution Micro-C maps identified a specialized class of regulatory DNAs termed 'tethering elements' (TEs) in Drosophila. These 300-500-bp elements facilitate specific long-range genomic associations or loops. The POZ-containing transcription factor GAF (GAGA-associated factor) contributes to loop formation. Tether-tether interactions accelerate Hox gene activation by distal enhancers, and coordinate transcription of duplicated genes (paralogs) through promoter-promoter associations. Some TEs engage in ultra-long-range enhancer-promoter and promoter-promoter interactions (meta-loops) in the Drosophila brain. We discuss the basis for tether-tether specificity and speculate on the occurrence of similar elements in vertebrate genomes.