Developmental genes in metazoan genomes are surrounded by dense clusters of 
conserved noncoding elements (CNEs). CNEs exhibit unexplained extreme levels of 
sequence conservation, with many acting as developmental long-range enhancers. 
Clusters of CNEs define the span of regulatory inputs for many important 
developmental regulators and have been described previously as genomic 
regulatory blocks (GRBs). Their function and distribution around important 
regulatory genes raises the question of how they relate to 3D conformation of 
these loci. Here, we show that clusters of CNEs strongly coincide with 
topological organisation, predicting the boundaries of hundreds of topologically 
associating domains (TADs) in human and Drosophila. The set of TADs that are 
associated with high levels of noncoding conservation exhibit distinct 
properties compared to TADs devoid of extreme noncoding conservation. The close 
correspondence between extreme noncoding conservation and TADs suggests that 
these TADs are ancient, revealing a regulatory architecture conserved over 
hundreds of millions of years.Metazoan genomes contain many clusters of 
conserved noncoding elements. Here, the authors provide evidence that these 
clusters coincide with distinct topologically associating domains in humans and 
Drosophila, revealing a conserved regulatory genomic architecture.