欧洲分子生物学实验室Eileen E. M. Furlong、Jan O. Korbel、Yad Ghavi-Helm团队取得一项新突破。他们的研究开发出了高度重组的染色体揭示了基因组拓扑结构和基因表达之间的解耦。 该研究于2019年8月发表于国际一流学术期刊《自然—遗传学》杂志上。

在这篇研究中，研究人员采用高度重排的染色体（平衡子）综合评估了基因组拓扑结构和基因表达之间的相互作用，这些染色体跨越了约75%的果蝇基因组。使用转基因（balancer品系/野生型）胚胎，课题组研究人员检测了拓扑结构中等位基因的特异性变化和顺式元件中基因的表达变化，同时尽量减少反式效应。通过基因组测序，该课题组研究人员解决了8个大型嵌套反转、较小反转、重复和数千个删除。这些广泛的重组引起了染色质拓扑结构的许多变化，破坏远程循环、拓扑关联域(TADs)和启动子相互作用。然而，这些并不能预测表达的变化。基因表达改变一般不发生在反转断点，这表明不适当的增强子启动子激活是一种罕见的事件。类似地，改变或融合TADs，改变TAD内连接和中断远程TAD间回路，不会改变大多数基因的表达。他们的研究结果表明，染色质拓扑结构以外的特性确保了高效增强子-启动子相互作用。

据了解，染色质拓扑结构与基因表达有着错综复杂的联系，但其功能性需求仍不清楚。

附：英文原文

Title: Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression

Author: Yad Ghavi-Helm, Aleksander Jankowski, Sascha Meiers, Rebecca R. Viales, Jan O. Korbel, Eileen E. M. Furlong

Issue&Volume: Volume 51 Issue 8

Abstract: Chromatin topology is intricately linked to gene expression, yet its functional requirement remains unclear. Here, we comprehensively assessed the interplay between genome topology and gene expression using highly rearranged chromosomes (balancers) spanning ~75% of the Drosophila genome. Using transheterozyte (balancer/wild-type) embryos, we measured allele-specific changes in topology and gene expression in cis, while minimizing trans effects. Through genome sequencing, we resolved eight large nested inversions, smaller inversions, duplications and thousands of deletions. These extensive rearrangements caused many changes to chromatin topology, disrupting long-range loops, topologically associating domains (TADs) and promoter interactions, yet these are not predictive of changes in expression. Gene expression is generally not altered around inversion breakpoints, indicating that mis-appropriate enhancerpromoter activation is a rare event. Similarly, shuffling or fusing TADs, changing intra-TAD connections and disrupting long-range inter-TAD loops does not alter expression for the majority of genes. Our results suggest that properties other than chromatin topology ensure productive enhancerpromoter interactions.

DOI: 10.1038/s41588-019-0462-3

Source:https://www.nature.com/articles/s41588-019-0462-3