biostudies-literatureKim IVEuropean Research Council1097-1105https://www.ebi.ac.uk/biostudies/studies/S-EPMC12221973biostudies-literatureUnknown642(8069)In bilaterian animals, gene regulation is shaped by a combination of linear and spatial regulatory information. Regulatory elements along the genome are integrated into gene regulatory landscapes through chromatin compartmentalization^1,2, insulation of neighbouring genomic regions^3,4 and chromatin looping that brings together distal cis-regulatory sequences⁵. However, the evolution of these regulatory features is unknown because the three-dimensional genome architecture of most animal lineages remains unexplored^6,7. To trace the evolutionary origins of animal genome regulation, here we characterized the physical organization of the genome in non-bilaterian animals (sponges, ctenophores, placozoans and cnidarians)^8,9 and their closest uNatureChromatin loops are an ancestral hallmark of the animal regulatory genome.PMC12221973851647950230Bykov NSMarti-Renom MAGrau-Bove XSuga HNavarrete CZolotarov GCanas-Armenteros Dde Mendoza AKim IVIglesias MBurkhardt PElek ASebe-Pedros ASoto-Angel JJKsiezopolska EMontgomery SALeys SPfalseChromatin loops are an ancestral hallmark of the animal regulatory genome.In bilaterian animals, gene regulation is shaped by a combination of linear and spatial regulatory information. Regulatory elements along the genome are integrated into gene regulatory landscapes through chromatin compartmentalization^1,2, insulation of neighbouring genomic regions^3,4 and chromatin looping that brings together distal cis-regulatory sequences⁵. However, the evolution of these regulatory features is unknown because the three-dimensional genome architecture of most animal lineages remains unexplored^6,7. To trace the evolutionary origins of animal genome regulation, here we characterized the physical organization of the genome in non-bilaterian animals (sponges, ctenophores, placozoans and cnidarians)^8,9 and their closest u2025-01-01T00:00:00Z2025 Jun2026-06-03T05:51:39.488Z2026-04-25T03:15:43.093ZS-EPMC122219734033569410.1038/s41586-025-08960-w