Evolution of 3D chromatin organization at different scales

Most animal genomes fold in 3D chromatin domains called topologically associated domains (TADs) that facilitate interactions between cis-regulatory elements (CREs) and promoters. Owing to their critical role in the control of developmental gene expression, we explore how TADs have shaped animal evolution. In the light of recent studies that profile TADs in disparate animal lineages, we discuss their phylogenetic distribution and the mechanisms that underlie their formation. We present evidence indicating that TADs are plastic entities composed of genomic strata of different ages: ancient cores are combined with newer regions and brought into extant TADs through genomic rearrangements. We highlight that newly incorporated TAD strata enable the establishment of new CRE-promoter interactions and in turn new expression patterns that can drive phenotypical innovation. We further highlight how subtle changes in chromatin folding may fine-tune the expression levels of developmental genes and hold a potential for evolutionary significance.