biostudies-literatureSchulten AEuropean Research CouncilMedical Research CouncilThe Royal SocietyWellcome TrustBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Council3321-3332.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618248biostudies-literatureUnknown85(17)Multivalent protein-chromatin interactions facilitated by higher-order protein assemblies are emerging as a crucial theme in eukaryotic gene regulation. However, understanding the underlying mechanisms in their functional context remains challenging. Arabidopsis VEL proteins assemble biomolecular condensates by head-to-tail polymerization. Here, we dissect the role of VEL polymerization domains in conferring the epigenetic switch to Polycomb repressive complex 2 (PRC2) silencing at Arabidopsis FLOWERING LOCUS C (FLC). We show that VIN3 VEL polymerization produces higher-order nuclear VIN3 assemblies in vivo, which promote multivalent chromatin association and efficient H3K27me3 nucleation. VRN5 VEL polymerization, however, is not required unless a third homolog VEL1 is absent. The VRN5 VELMolecular cellVEL-dependent polymerization maintains the chromatin association of Polycomb proteins for the switch to epigenetic silencing.PMC7618248EPISWITCH-833254MC_U105192713MC_U105192715833254EP/W024063/1RP\\R1\\180002BB/P013511/1BB/J004588/1225217/Z/22/Z210654/Z/18/ZEP/T002166/1EP/T00214X/1210654Jang GJLeake MCDean CSchulten APayne-Dwyer AFiedler MBienz MNielsen MLMateo-Bonmati EfalseVEL-dependent polymerization maintains the chromatin association of Polycomb proteins for the switch to epigenetic silencing.Multivalent protein-chromatin interactions facilitated by higher-order protein assemblies are emerging as a crucial theme in eukaryotic gene regulation. However, understanding the underlying mechanisms in their functional context remains challenging. Arabidopsis VEL proteins assemble biomolecular condensates by head-to-tail polymerization. Here, we dissect the role of VEL polymerization domains in conferring the epigenetic switch to Polycomb repressive complex 2 (PRC2) silencing at Arabidopsis FLOWERING LOCUS C (FLC). We show that VIN3 VEL polymerization produces higher-order nuclear VIN3 assemblies in vivo, which promote multivalent chromatin association and efficient H3K27me3 nucleation. VRN5 VEL polymerization, however, is not required unless a third homolog VEL1 is absent. The VRN5 VEL2025-01-01T00:00:00Z2025 Sep2026-06-04T11:02:15.389Z2026-05-08T03:10:57.936ZS-EPMC76182484085811210.1016/j.molcel.2025.08.002