The 3D architecture of the genome influences gene regulation through topologically associating domains (TADs), which ensure that promoters and enhancers can interact. Although the importance of these TADs is well known, the direct effects on gene expression have been less well described. Now, Rafael Galupa, Edith Heard and colleagues use the genetic landscape around the mouse X-inactivation centre, which contains the Xist and Tsix non-coding RNA loci, to dissect the effect of rearranging TADs on gene expression. The authors invert most of the Tsix-TAD and find that new but similar contact hotspots are formed within the TAD, but there is a reduction in the long-range contacts with the adjacent Xist-TAD, due to apparent differences in ‘strength’ of the inverted CCCTC-binding factor (CTCF) sites. They identify limited transcriptional changes in genes within the Tsix-TAD, while expression of Xist in the neighbouring TAD is upregulated. Manipulation of clusters of CTCF sites within the Tsix-TAD have similar effects on gene expression. Together, these data show that topological rearrangements can have limited effect on gene expression within a TAD but can exert a bigger influence in a neighbouring TAD, indicating a role of inter-TAD communication.