Multiple transactivation domains of EZH2 bind to the TAZ2 domain of p300 and stimulate the acetyltransferase function of p300
Bibliographic record
Abstract
The H3K27me-specific methyltransferase enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of the repressive complex Polycomb repressive complex 2. EZH2 is typically implicated in transcriptional silencing, but it can also activate gene expression. Here, we show that EZH2 contains three adjacent transactivation domains (EZH2TAD) that are recognized by the TAZ2 domain of the transcriptional coactivator and acetyltransferase p300 (p300TAZ2). Binding interfaces identified by chemical shift perturbations in NMR experiments, measurements of binding affinities, and analysis of the complex formation by mass photometry demonstrate that each EZH2TAD can be concomitantly bound by a separate p300TAZ2. Interaction of EZH2TADs with p300TAZ2 stimulates H3K18- and H3K27-specific acetyltransferase activity of p300. We show that in 22Rv1 prostate cancer cells, EZH2 occupies a large set of gene loci lacking H3K27me3, and these non-canonical genomic sites are instead co-occupied by p300, RNA Polymerase II and BRD4 and are rich in histone marks associated with transcriptional activation. Our findings shed light on the potential basis for such a high degree of genetic co-localization through the direct association of p300TAZ2 with EZH2TADs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".