GEO series

Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes [Cut & Run, Cut & Tag]

GSE318276 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2026/02/05 Platform GPL24247

Summary

Phase separation is increasingly recognized in facultative heterochromatinization of Polycomb target genes; however, the underlying mechanisms remain obscure. Using single-molecule imaging and tracking, we show that individual condensates in mESCs contain approximately 3 CBX2 molecules and numerous PRC1 and PRC2 subunits and indicate that the composition and dynamics of condensates are developmentally regulated. We reveal that CBX2 clusters PRC2 and controls the spatial distribution of both PRC2 and H3K27me3. Using genomic approaches, we demonstrate that CBX2 binds condensate initiation sites enriched for PRC2 nucleation sites. CBX2 deletion causes PRC2 and H3K27me3 to redistribute from their regular targets. By developing a separate-of-function variant, we determine that CBX2 relies on its self-clustering ability to function. These findings collectively support a novel phase-separation model driven by nucleation and bridging, in which low-abundance proteins self-cluster to initiate condensate assembly, a process tightly coupled to function.

Published in

Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes

Ingersoll S, Trouth A, Angel JC et al. · Molecular cell 2026 · PMID 41785860 · doi:10.1016/j.molcel.2026.02.009

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Also filed as BioProject PRJNA1418516 and SRA study SRP674380. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41785860) ↗

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