法国居里研究所的Edith Heard研究组合作发现，对Xic的分型拓扑相关结构域的组建参与发育过程中Tsix和Xist的双向调控。该项研究成果发表在2019年6月出版的《Nature Genetics》上。

首先，研究人员交换了Xist/Tsix两者的转录单位，并将其各自的启动子替换到了对方的TAD。实验结果表明，这种改变交换了两者的表达模式：在雄性和雌性的多潜能干细胞中，Xist的表达变得提前并异位上调；而Tsix的表达在分化过程中展现出异常的持续。因此，Xic的拓扑分区对于确保发育过程中X染色体精确地失活是至关重要的。这项研究揭示了顺式调控景貌的基因组结构能够影响哺乳动物的发育过程。

据悉，小鼠的X染色体失活中心（Xic）基因座是研究基因组结构与基因调控的有力模型。这是因为尽管存在于一个重合的正义/反义单元中，非编码基因Xist和Tsix在发育过程中却呈相反的表达模式。Xic被组建成两种拓扑相关结构域（TAD），但这些结构是如何编排这些顺式调控信息的却尚不清楚。

附：英文原文

Title: The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

Author: Joke G. van Bemmel, Rafael Galupa, Chris Gard, Nicolas Servant, Christel Picard, James Davies, Anthony James Szempruch, Yinxiu Zhan, Jan J. ylicz, Elphge P. Nora, Sonia Lameiras, Elzo de Wit, David Gentien, Sylvain Baulande, Luca Giorgetti, Mitchell Guttman, Jim R. Hughes, Douglas R. Higgs, Joost Gribnau, Edith Heard

Issue&Volume: Volume 51 Issue 6, June 2019

Abstract: The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each others TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes.

DOI: 10.1038/s41588-019-0412-0

Source:https://www.nature.com/articles/s41588-019-0412-0