This study was made possible by fantastic collaborations within the @heardlab.bsky.social and beyond. Huge thanks and congratulations to everyone who contributed! 🤩🤩🤩🎉🎉🎉🥳🥳🥳 @odomlab.bsky.social @oliverstegle.bsky.social @howardychang.bsky.social @JudithZaugg

We propose that natural fluctuations in Xist RNA levels - during development, in adult tissues, or disease - tune escapee gene dosage, laying the groundwork to explore Xist as a molecular signature of X-linked gene mis-regulation in health and disease.

Xist-mediated repression of escapees is SPEN-dependent and reshapes Xi 3D organization: TAD-like domains over escapee clusters are lost upon silencing and re-emerged when transcription resumes.

We show that increasing levels of Xist RNA repress escapee genes, well beyond early development, in differentiated, non-dividing cells and in vivo post implantation embryos.