Polycomb-to-Trithorax Switch at Synaptic Plasticity Genes
Curated pathway from expert analysis
flowchart TD
A["PRC2 Polycomb Repressive Complex<br/>EZH2 H3K27me3 CBX Proteins"]
B["H3K27me3 Deposition<br/>Synaptic Plasticity Gene Repression"]
C["Activity-Dependent Epigenetic Switch<br/>KMT2D Trithorax Complex Recruitment"]
D["H3K4me3 Activation Mark<br/>Gene Derepression at Synaptic Loci"]
E["BDNF and ARC Expression<br/>Synaptic Plasticity Restoration"]
F["Cognitive Resilience<br/>Long-Term Potentiation Maintenance"]
G["PRC2 Overactivation<br/>Excessive H3K27me3 Blocks Plasticity Genes"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"blocks"| C
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for POLYCOMB-TO-TRITHORAX yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for Polycomb-to-Trithorax Switch at.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we administer the EZH2 inhibitor GSK126 (50 mg/kg, i.p., daily for 21 days) to 5xFAD transgenic mice (an Alzheimer's disease model), THEN we will observe enhanced histone H3K4me3 at synaptic plasti | Increased H3K4me3/H3K27me3 ratio at plasticity gene promoters, elevated Arc and Egr1 protein levels in hippocampus, and ≥20% improvement in spatial memory acqui | — no observation — | pending | 0.45 |
| IF we perform chromatin immunoprecipitation sequencing (ChIP-seq) for H3K27me3 and H3K4me3 at synaptic plasticity gene promoters in hippocampal tissue from aged mice (18 months) compared to young adul | Decreased H3K27me3 (Polycomb mark) and increased H3K4me3 (Trithorax mark) at synaptic plasticity gene promoters with corresponding increased mRNA expression of | — no observation — | pending | 0.55 |