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

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 other's 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 aberran

SUBMITTER: van Bemmel JG 

PROVIDER: S-EPMC6551226 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature