The bipartite structure of the X-inactivation center is responsible for regulating the Tsix and Xist genes during development, according to the work conducted by Dr. Joke van Bemmel and Dr. Rafael Galupa in the team of Prof. Edith Heard in Nature Genetics.
The X-inactivation center locus in mice is a powerful model for understanding the links between genome architecture and gene regulation, with the Xist and Tsix non-coding genes showing opposing expression patterns throughout development, despite being organized into an overlapping sense-antisense pair.
The X-inactivation center (Xic) is organized as two topologically associating domains (TADs), but the role of this organization is unclear. To further investigate this, a team of researchers from Institut Curie, overseen by Edith Heard, created inversions in the genome to permute the Xist/Tsix transcriptional unit and put their promoters in the TAD of each other. In doing so, they discovered that this led to an inversion in their expression patterns: Xist became positively regulated early on in male and female pluripotent cells alike, while Tsix aberrantly remains expressed upon differentiation.
This means that topological partitioning of the Xic is key to ensure proper X-inactivation. Conducted in collaboration with laboratories in Rotterdam, Oxford, Pasadena, Basel and Amsterdam, and with the support of Institut Curie’s platforms, this study shows how gene architecture in cis-regulatory sites can impact on regulating growth in mammals.
Rotterdam, Gribnau Group
Oxford, Higgs and Hughes Groups
Pasadena, Guttman Group
Basel, Giorgetti Group