The role of insulators and transcription in 3D chromatin organization of flies
- Keerthi T. Chathoth1,6,7,
- Liudmila A. Mikheeva1,2,3,6,
- Gilles Crevel4,
- Jareth C. Wolfe1,2,5,
- Ioni Hunter1,
- Saskia Beckett-Doyle1,
- Sue Cotterill4,
- Hongsheng Dai3,
- Andrew Harrison3 and
- Nicolae Radu Zabet1,2
- 1School of Life Sciences, University of Essex, Colchester CO4 3SQ, United Kingdom;
- 2Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom;
- 3Department of Mathematical Sciences, University of Essex, Colchester CO4 3SQ, United Kingdom;
- 4Department Basic Medical Sciences, St. Georges University London, London SW17 0RE, United Kingdom;
- 5School of Computer Science and Electronic Engineering, University of Essex, Colchester CO4 3SQ, United Kingdom
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↵6 These authors contributed equally to this work.
Abstract
The DNA in many organisms, including humans, is shown to be organized in topologically associating domains (TADs). In Drosophila, several architectural proteins are enriched at TAD borders, but it is still unclear whether these proteins play a functional role in the formation and maintenance of TADs. Here, we show that depletion of BEAF-32, Cp190, Chro, and Dref leads to changes in TAD organization and chromatin loops. Their depletion predominantly affects TAD borders located in regions moderately enriched in repressive modifications and depleted in active ones, whereas TAD borders located in euchromatin are resilient to these knockdowns. Furthermore, transcriptomic data has revealed hundreds of genes displaying differential expression in these knockdowns and showed that the majority of differentially expressed genes are located within reorganized TADs. Our work identifies a novel and functional role for architectural proteins at TAD borders in Drosophila and a link between TAD reorganization and subsequent changes in gene expression.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.275809.121.
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Freely available online through the Genome Research Open Access option.
- Received May 26, 2021.
- Accepted February 17, 2022.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
