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.

中文翻译：

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绝缘体和转录在果蝇 3D 染色质组织中的作用

包括人类在内的许多生物体中的 DNA 被证明是按照拓扑关联域 (TAD) 组织的。在果蝇, 几种结构蛋白在 TAD 边界富集，但尚不清楚这些蛋白质是否在 TAD 的形成和维持中发挥功能作用。在这里，我们展示了 BEAF-32、Cp190、Chro 和 Dref 的消耗导致 TAD 组织和染色质环的变化。它们的消耗主要影响位于适度富含抑制性修饰和耗尽活性修饰区域的 TAD 边界，而位于常染色质中的 TAD 边界对这些击倒具有弹性。此外，转录组数据揭示了数百个基因在这些敲低中表现出差异表达，并表明大多数差异表达基因位于重组的 TAD 内。我们的工作确定了 TAD 边界的结构蛋白在果蝇和 TAD 重组与随后的基因表达变化之间的联系。