SET7/9 exhibits sigmoidal kinetics on nucleosomes, hyperbolic kinetics on histones by an ordered sequential mechanism, and methylates lysine and arginine
Bibliographic record
Abstract
SET7/9 (SETD7) is a SET domain protein lysine methyltransferase (PKMT). We characterized its activity using a mass spectrometry (MS) assay, showing that it follows an ordered sequential enzyme kinetic mechanism where SAM is the first substrate to bind, followed by histone H3, and mono-methylated histone H3 is the first product to dissociate, followed by SAH. Full-length histones H2A, H2B, and H4 are also substrates for SET7/9. We found that SET7/9 methylates nucleosome core particles (NCP), histone H2BK120 ubiquitinated nucleosome core particles (Ub-NCP) as well as histone octamers, exhibiting sigmoidal kinetics, and suggesting an allosteric interaction that was not observed with free histones, which follow hyperbolic (Michaelis-Menten) kinetics. Using low (25 nM) SET7/9, we only detect monomethyl-lysine with all substrates except Ub-NCP, which produces mono- and di-methyllysine at equal rates. Proteomic analysis shows that SET7/9 catalyzes multiple sites and types of, methylation on histones, depending on if they are free histones, or within an octamer. Free histone H3 is methylated at multiple N-terminal sites (including H3K4) that are not methylated in the octamer. Some C-terminal methylation sites were discovered that can also be ubiquitinated including H2BK120. Since lysine methylation and ubiquitination are mutually exclusive such methylation by SET7/9 may serve to prevent ubiquitination. At high enzyme and substrate concentrations and extended incubation times, we show that SET7/9 can catalyze the formation of dimethyl- and trimethyllysine on H2B, H3 and histone octamers and, most remarkably, the formation of monomethyl- and dimethylarginine on histone H3 and within octamers.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 0.000 |
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 teacher head, 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".