- PRC2 silences genes by adding H3K27me3 at the right spots in the genome. Our model shows how the nucleic acid-binding domain (NBD) of SUZ12 keeps this activity under control, and what happens when you remove it.
- Wild-type SUZ12: much of PRC2 can interact with RNA (large red bubble), which blocks engagement with nucleosomes. Accessory subunits (PRC2.1/2.2) target CpG islands. Result: strong H3K27me3 at intended sites, little elsewhere. Arrow size = rate. Bubble size = how much PRC2 is in that state.
- ncMUT: PRC2 still binds RNA efficiently (large red bubble, large red arrows), so catalysis stays limited. But without accessory subunits, PRC2 targeting is unfocused. Result: most PRC2 remains in the RNA-bound state, with little productive methylation at CpG islands.Aug 13, 2025 21:53
- VEFS: the NBD is gone. RNA binding is rare (small red bubble). Most PRC2 is RNA-free, catalytically active, and binds both CpG and non-CpG sites. Result: diffuse H3K27me3 that dilutes PRC1 away from its normal targets, disrupting gene silencing. Read more in our preprint: tinyurl.com/4yrwftrn