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

Autor: Messina, Olivier, Raynal, Flavien, Gurgo, Julian, Fiche, Jean-Bernard, Pancaldi, Vera, Nollmann, Marcelo
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Zdroj: Nature Communications; 10/21/2023, Vol. 14 Issue 1, p1-14, 14p
Abstrakt: 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. In Drosophila, insulators may be involved in the organization of Topological Associated Domains, but the mechanism of action is a still a matter of investigation. Here the authors investigate the role of insulators in the 3D organization of the Drosophila genome by combining bioinformatics analysis and Hi-M, an imaging-based methods developed to detect the 3D positions of multiple genomic loci in single cells. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index