Year: 2026
Type: preprint
Abstract: X chromosome inactivation in mammals is driven by the long non-coding RNA Xist, which localizes and spreads across the chromosome from which it is transcribed. Although several factors required for Xist localization have been identified, the underlying mechanism remains unclear. Here, we combine Nuclear-BRITE, a method for visualizing and quantifying the dynamics of individual Xist RNA molecules, with acute depletion of candidate localization factors. We find that Xist molecules remain constrained throughout interphase, consistent with continuous association with chromatin. Building on this observation, we identify a contact-mediated transfer mechanism in which 3D chromosome dynamics promote handover of Xist molecules between chromosomal sites. We further show that the Xist-binding proteins SPEN and HNRNPU play distinct roles in this process by promoting Xist–Xist and Xist–chromatin interactions, respectively. Together, our findings define a mechanism for Xist RNA spreading and provide a framework for understanding its unique chromosome-wide localization.
Institution: University of Oxford
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Micron Oxford: super-resolution imaging of cellular dynamics., Micron Oxford: super-resolution imaging of cellular dynamics., X chromosome inactivation; linking mechanisms for in cis accumulation of Xist RNA and chromosome silencing., X chromosome inactivation; linking mechanisms for in cis accumulation of Xist RNA and chromosome silencing., Advanced Microscopy for Chromosome and RNA Dynamics.
OpenAlex ID: W7220391438