Structural Insights into the Role of PHD Fingers in the MOZ/MORF and HBO1 HATs
Bibliographic record
Abstract
The MOZ/MORF and HBO1 histone acetyltransferases (HATs) are important for regulation of many cellular processes including transcription activation, DNA repair and development. They form multi‐subunit complexes that contain several distinct plant‐homeodomains (PHD). PHD fingers were originally discovered to bind post‐transcriptional modifications (PTMs) on the histone H3 tail, particularly tri‐methylation at lysine 4 (H3K4me3). Current research indicates PHD fingers are divided into functional classes that bind other PTMs as well. The ING4, ING5, BRPF1 and Jade1 subunits of MOZ/MORF and HBO1 all harbor PHD fingers, however, the functional role of these PHD modules has not been determined. We aimed to elucidate the different substrate specificity and function of PHD fingers within MOZ/MORF and HBO1 towards histone tails using X‐ray crystallography, NMR, fluorescence spectroscopy and mutagenesis. Here we report the crystal structures of ING4 and ING5 in complex with the H3K4me3 histone peptide, the binding of Jade1 and BRPF1 to the unmodified H3 tail, and affinities of the PHD finger:histone interaction. Functional analysis indicates both the ING4/5 subunits and methylated H3K4 regulate enzymatic activity. Together these studies provide an essential link between HAT activity and chromatin remodeling, and impart a greater understanding on how the histone code is read.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".