Bivalent Domain Resolution as Stimulus Decoder
🧪 Overview
Bivalent chromatin domains (co-occurrence of H3K4me3 and H3K27me3) maintained by polycomb/trithorax complexes act as stimulus decoders. Upon signaling, these domains resolve toward activation or repression depending on the specific kinase/phosphatase activity and which histone methyltransferase/histone demethylase is recruited. This provides a mechanistic explanation for stimulus-specificity: the same activating signal may trigger H3K27me3 demethylation at one bivalent locus (activating transcription) while remaining inert at another bivalent domain where co-repressive complexes persist.
🧬 Mechanism
Auto-built from this analysis's top knowledge-graph edges.
graph TD
XIST["XIST"] -->|causes| X_chromosome_silencing["X-chromosome silencing"]
KDM6B["KDM6B"] -->|regulates| H3K27me3_demethylation["H3K27me3 demethylation"]
Super_Enhancers["Super-Enhancers"] -->|activates| signal_integration["signal integration"]
BRD4["BRD4"] -->|regulates| super_enhancer_driven_onc["super-enhancer-driven oncogenes"]
CTCF["CTCF"] -->|associated with| insulated_neighborhoods["insulated neighborhoods"]
CTCF_1["CTCF"] -->|associated with| chromatin_remodeling_reac["chromatin remodeling reach"]
lncRNAs["lncRNAs"] -->|associated with| chromatin_remodeling_comp["chromatin remodeling complexes"]
phase_separation["phase separation"] -->|regulates| super_enhancer_signal_amp["super-enhancer signal amplification"]
KDM6B_2["KDM6B"] -->|regulates| H3K27me3["H3K27me3"]
Super_Enhancers_3["Super-Enhancers"] -->|regulates| cell_identity_genes["cell identity genes"]
FOXA1["FOXA1"] -->|regulates| Chromatin_Accessibility["Chromatin Accessibility"]
PU_1["PU.1"] -->|regulates| Chromatin_Accessibility_4["Chromatin Accessibility"]
style XIST fill:#ce93d8,stroke:#333,color:#000
style X_chromosome_silencing fill:#4fc3f7,stroke:#333,color:#000
style KDM6B fill:#ce93d8,stroke:#333,color:#000
style H3K27me3_demethylation fill:#4fc3f7,stroke:#333,color:#000
style Super_Enhancers fill:#4fc3f7,stroke:#333,color:#000
style signal_integration fill:#4fc3f7,stroke:#333,color:#000
style BRD4 fill:#ce93d8,stroke:#333,color:#000
style super_enhancer_driven_onc fill:#4fc3f7,stroke:#333,color:#000
style CTCF fill:#ce93d8,stroke:#333,color:#000
style insulated_neighborhoods fill:#4fc3f7,stroke:#333,color:#000
style CTCF_1 fill:#ce93d8,stroke:#333,color:#000
style chromatin_remodeling_reac fill:#4fc3f7,stroke:#333,color:#000
style lncRNAs fill:#ce93d8,stroke:#333,color:#000
style chromatin_remodeling_comp fill:#4fc3f7,stroke:#333,color:#000
style phase_separation fill:#4fc3f7,stroke:#333,color:#000
style super_enhancer_signal_amp fill:#4fc3f7,stroke:#333,color:#000
style KDM6B_2 fill:#ce93d8,stroke:#333,color:#000
style H3K27me3 fill:#4fc3f7,stroke:#333,color:#000
style Super_Enhancers_3 fill:#4fc3f7,stroke:#333,color:#000
style cell_identity_genes fill:#4fc3f7,stroke:#333,color:#000
style FOXA1 fill:#4fc3f7,stroke:#333,color:#000
style Chromatin_Accessibility fill:#4fc3f7,stroke:#333,color:#000
style PU_1 fill:#ce93d8,stroke:#333,color:#000
style Chromatin_Accessibility_4 fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — KDM6B
No curated PDB or AlphaFold mapping for KDM6B yet. Search RCSB →
💉 Clinical Trials
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 KDM6B (JMJD3), EZH2, UTX, RNF20.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_round_mining
| source | v1_phase_c_backfill |
| origin_type | debate_round_mining |
| _schema_version | 1 |