ABSTRACT
Transposable elements (TEs) shape genome regulation by harboring regulatory factor binding sites—including CTCF-binding sites known to tether chromatin loops and mark domain boundaries. The mechanisms underlying the emergence and evolution of these 3D genome structures remain unprobed. We find that TEs contribute extensively to emergence of species-specific loops in humans and mice by depositing novel anchor CTCF motifs, as well as to maintenance of conserved loops via CTCF binding site turnover. Deleting such TEs in human cells leads to collapse of conserved 3D structures. TEs have long been considered a source of genetic innovation; by comparing topologies, we show that TEs contribute regulatory plasticity that helps maintain conserved genome architecture—revealing a new paradigm for defining noncoding, regulatory conservation beyond classic DNA sequence preservation.
One-sentence summary Co-option of transposable elements maintains conserved 3D genome structures via CTCF binding site turnover in human and mouse.
