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A biophysical basis for the spreading behavior and limited diffusion of Xist [RNA-Seq]

GSE273563 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/01/17 Platform GPL24247
Summary
Here we reveal a biophysical basis for the spreading behavior of Xist RNA on the inactive X-chromosome (Xi). Xist and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the Xi. HNRNPK and Xist exert mutual pulling forces that lead to RNA internalization into the condensate. While HNRNPK is sufficient for condensate formation, Xist induces a further phase transition into a "soft" droplet by altering elasticity, adhesiveness, and wetting properties of the condensate in vitro. Once phase transition occurs, other Xist-interacting factors are internalized and concentrated within the condensate. We attribute LLPS to HNRNPK's RGG and Xist's Repeat B (RepB) motifs. Mutating these motifs causes Xist diffusion, disrupts Polycomb recruitment, and precludes the required mixing of Xi chromatin for establishing the Xi superstructure. Thus, phase transitions driven by RepB and HNRNPK create a membrane-less subnuclear compartment for the localization and limited diffusion of Xist ribonucleoprotein complexes on the Xi.
Published in
A biophysical basis for the spreading behavior and limited diffusion of Xist
Ding M, Wang D, Chen H et al. · Cell 2025 · PMID 39824183 · doi:10.1016/j.cell.2024.12.004
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Also filed as BioProject PRJNA1142420 and SRA study SRP523321. Searching any of these in the dataset finder brings you back here.

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