FRIGIDA-dependent FLC activation and vernalization-induced Polycomb silencing of FLC

In winter-annual Arabidopsis thaliana accessions, the plant-specific scaffold protein FRIGIDA (FRI) assembles the FRI-C transcription activator complex (with SUF4, FLX, FES1 and FRL1) at the FLOWERING LOCUS C (FLC) promoter. FRI-C recruits H3K4 and H3K36 methyltransferase and H2A.Z exchange activities and the nuclear cap-binding complex, raising expression of the MADS-box floral repressor FLC. FLC, with its partner SVP, represses the floral integrators FT (in leaves) and SOC1 (in the meristem), so flowering is blocked before winter. Prolonged cold (vernalization) overcomes this block in two mechanistically separate phases. (1) Nucleation: the slow, quantitative cold induction of the VEL protein VIN3 is the molecular readout of the length of winter. VIN3 heterodimerizes through its VEL domain with the constitutively expressed VRN5 (VIL1), which bridges it to a VRN2-containing PRC2 core (SWN/CLF, FIE, MSI1). The resulting PHD-PRC2 is targeted to a three-nucleosome nucleation region near the first exon-intron boundary of FLC, where the sequence-specific repressor VAL1 also binds. VIN3 VEL-domain head-to-tail polymerization builds multivalent assemblies that nucleate H3K27me3, switching individual FLC alleles digitally into a metastable silenced state. (2) Spreading and maintenance: after return to warmth, H3K27me3 spreads over the whole FLC locus in a step that needs CLF-PRC2 and LHP1, and the chromatin-associated, sequence-nonspecific DNA-binding B3 protein VRN1 is needed to keep FLC stably silenced through later development. Silencing of FLC de-represses FT and SOC1, so flowering follows in spring. The autonomous pathway (FCA, FPA, FLD, FVE, FY, LD), which represses FLC independently of cold, COOLAIR antisense transcription, and resetting of FLC in each generation are outside this module.

Boundary: the autonomous pathway (FCA, FPA, FY, FLD, FVE, LD), which represses FLC independently of cold, is a separate module and is not modelled here. Cold also acts on the activation step: it promotes FRI nuclear condensates and lowers FRI occupancy at FLC (PMID:34732891, the subject of a Matters Arising exchange). This is recorded in prose rather than as a connection because there is no separate cold-sensing node. COOLAIR antisense transcription, the FLC nucleation-region cis-element and generational resetting of FLC are out of scope. No production GO-CAMs in gocams/index.tsv contain these Arabidopsis proteins. Gene reviews for FRI (functional allele P0DH90), VIN3, VRN5/VIL1, VRN2 and VRN1 were written together with this module, followed by CLF, SWN (EZA1), FIE and MSI1. LHP1, VAL1 and SVP have their own gene reviews, and every UniProt grounding in the module now has a completed review.