GCN5 Maintains Muscle Integrity by Acetylating YY1 to Promote Dystrophin Expression
Bibliographic record
Abstract
Abstract This work identifies a novel role for the acetyltransferase GCN5 in regulating muscle integrity through inhibition of DNA binding activity of the transcriptional repressor YY1. Here we report that in mice a muscle-specific knockout of GCN5 ( Gcn5 skm-/- ) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. Supporting our observation, a meta-analysis between the differential transcriptome of Gcn5 skm-/- muscle and all available open-access data sets identified top correlations with musculoskeletal diseases in humans. GCN5 was found to acetylate YY1 at two residues (K392 and K393), which disrupts the interaction between the YY1 zinc-finger region and DNA. De/acetylation mimics for these YY1 post-translational modifications modulated muscle structural gene expression and DNA binding. Analysis of human GTEx data also found positive and negative correlations between fiber diameter and GCN5 and YY1 respectively. Collectively, our results demonstrate that GCN5 acetyltransferase activity regulates YY1 DNA binding and expression of dystrophin to modulate muscle integrity.
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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 | 0.001 |
| 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) | 0.002 | 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".