Topologically associated domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation

In vertebrates and other Metazoa, developmental genes are found surrounded by dense clusters of highly conserved noncoding elements (CNEs). CNEs exhibit extreme levels of sequence conservation of unexplained origin, with many acting as long-range enhancers during development. Clusters of CNEs, termed genomic regulatory blocks (GRBs), define the span of regulatory interactions for many important developmental regulators. The function and genomic distribution of these elements close to important regulatory genes raises the question of how they relate to the 3D conformation of these loci. We show that GRBs, defined using clusters of CNEs, coincide strongly with the patterns of topological organ