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Epigenetic regulation by dynamic RNA G-quadruplex folding and unfolding (RNA-Seq)

GSE219081 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/05/17 Platform GPL24247
Summary
Whether RNA G-quadruplexes (rG4) form extensively in vivo and what roles they play remain actively debated. Among their proposed functions is recognition of Polycomb repressive complex 2 (PRC2), but how the interaction results in epigenetic regulation is not understood. Here we demonstrate that rG4s form dynamically during ES cell differentiation and require ATRX’s helicase function to unwind competing secondary structures. Mutating ATRX causes rG4 depletion on a transcriptome-wide basis and dramatically increases gene expression. We identify and mutate rG4s within Xist RNA and mechanistically separate PRC2’s recruitment versus catalysis. Surprisingly, although rG4s recruit PRC2, unfolding the rG4 structure causes PRC2 hyperactivation, entrapment of PRC2 in the S1 chromosomal compartment, and loss of gene silencing. Thus, we link dynamic rG4 folding and unfolding to PRC2 recruitment, trans-compartmental Xist migration, regulated activation of PRC2, and whole-chromosome gene silencing.
Published in
G-quadruplex folding in Xist RNA antagonizes PRC2 activity for stepwise regulation of X chromosome inactivation
Lee YW, Weissbein U, Blum R et al. · Molecular cell 2024 · PMID 38759625 · doi:10.1016/j.molcel.2024.04.015
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Also filed as BioProject PRJNA907003 and SRA study SRP410676. Searching any of these in the dataset finder brings you back here.

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