Chromatin loops are an ancestral hallmark of the animal regulatory genome

Iana V. Kim (), Cristina Navarrete, Xavier Grau-Bové, Marta Iglesias, Anamaria Elek, Grygoriy Zolotarov, Nikolai S. Bykov, Sean A. Montgomery, Ewa Ksiezopolska, Didac Cañas-Armenteros, Joan J. Soto-Angel, Sally P. Leys, Pawel Burkhardt, Hiroshi Suga, Alex Mendoza, Marc A. Marti-Renom and Arnau Sebé-Pedrós ()
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Iana V. Kim: Barcelona Institute of Science and Technology (BIST)
Cristina Navarrete: Barcelona Institute of Science and Technology (BIST)
Xavier Grau-Bové: Barcelona Institute of Science and Technology (BIST)
Marta Iglesias: Barcelona Institute of Science and Technology (BIST)
Anamaria Elek: Barcelona Institute of Science and Technology (BIST)
Grygoriy Zolotarov: Barcelona Institute of Science and Technology (BIST)
Nikolai S. Bykov: Centre Nacional d’Anàlisis Genòmic (CNAG)
Sean A. Montgomery: Barcelona Institute of Science and Technology (BIST)
Ewa Ksiezopolska: Barcelona Institute of Science and Technology (BIST)
Didac Cañas-Armenteros: Barcelona Institute of Science and Technology (BIST)
Joan J. Soto-Angel: University of Bergen
Sally P. Leys: University of Alberta
Pawel Burkhardt: University of Bergen
Hiroshi Suga: Prefectural University of Hiroshima
Alex Mendoza: Queen Mary University of London
Marc A. Marti-Renom: Barcelona Institute of Science and Technology (BIST)
Arnau Sebé-Pedrós: Barcelona Institute of Science and Technology (BIST)

Nature, 2025, vol. 642, issue 8069, 1097-1105

Abstract: Abstract 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 compartmentalization1,2, insulation of neighbouring genomic regions3,4 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 unexplored6,7. 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 unicellular relatives (ichthyosporeans, filastereans and choanoflagellates)10 by combining high-resolution chromosome conformation capture11,12 with epigenomic marks and gene expression data. Our comparative analysis showed that chromatin looping is a conserved feature of genome architecture in ctenophores, placozoans and cnidarians. These sequence-determined distal contacts involve both promoter–enhancer and promoter–promoter interactions. By contrast, chromatin loops are absent in the unicellular relatives of animals. Our findings indicate that spatial genome regulation emerged early in animal evolution. This evolutionary innovation introduced regulatory complexity, ultimately facilitating the diversification of animal developmental programmes and cell type repertoires.

Date: 2025
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DOI: 10.1038/s41586-025-08960-w

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