3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription

Olivier Messina, Flavien Raynal, Julian Gurgo, Jean-Bernard Fiche, Vera Pancaldi () and Marcelo Nollmann ()
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Olivier Messina: Univ Montpellier, CNRS UMR 5048, INSERM U1054
Flavien Raynal: Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse
Julian Gurgo: Univ Montpellier, CNRS UMR 5048, INSERM U1054
Jean-Bernard Fiche: Univ Montpellier, CNRS UMR 5048, INSERM U1054
Vera Pancaldi: Université de Toulouse, Inserm, CNRS, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse
Marcelo Nollmann: Univ Montpellier, CNRS UMR 5048, INSERM U1054

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract In mammals, insulators contribute to the regulation of loop extrusion to organize chromatin into topologically associating domains. In Drosophila the role of insulators in 3D genome organization is, however, under current debate. Here, we addressed this question by combining bioinformatics analysis and multiplexed chromatin imaging. We describe a class of Drosophila insulators enriched at regions forming preferential chromatin interactions genome-wide. Notably, most of these 3D interactions do not involve TAD borders. Multiplexed imaging shows that these interactions occur infrequently, and only rarely involve multiple genomic regions coalescing together in space in single cells. Finally, we show that non-border preferential 3D interactions enriched in this class of insulators are present before TADs and transcription during Drosophila development. Our results are inconsistent with insulators forming stable hubs in single cells, and instead suggest that they fine-tune existing 3D chromatin interactions, providing an additional regulatory layer for transcriptional regulation.

Date: 2023
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DOI: 10.1038/s41467-023-42485-y

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