MyoD- and nerve-dependent maintenance of MyoDexpression in mature muscle fibres acts through the DRR/PRR element
Bibliographic record
Abstract
BACKGROUND: MyoD is a transcription factor implicated in the regulation of adult muscle gene expression. Distinguishing the expression of MyoD in satellite myoblasts and muscle fibres has proved difficult in vivo leading to controversy over the significance of MyoD expression within adult innervated muscle fibres. Here we employ the MD6.0-lacZ transgenic mouse, in which the 6 kb proximal enhancer/promoter (DRR/PRR) of MyoD drives lacZ, to show that MyoD is present and transcriptionally active in many adult muscle fibres. RESULTS: In culture, MD6.0-lacZ expresses in myotubes but not myogenic cells, unlike endogenous MyoD. Reporter expression in vivo is in muscle fibre nuclei and is reduced in MyoD null mice. The MD6.0-lacZ reporter is down-regulated both in adult muscle fibres by denervation or muscle disuse and in cultured myotubes by inhibition of activity. Activity induces and represses MyoD through the DRR and PRR, respectively. During the postnatal period, accumulation of beta-galactosidase correlates with maturation of innervation. Strikingly, endogenous MyoD expression is up-regulated in fibres by complete denervation, arguing for a separate activity-dependent suppression of MyoD requiring regulatory elements outside the DRR/PRR. CONCLUSION: The data show that MyoD regulation is more complex than previously supposed. Two factors, MyoD protein itself and fibre activity are required for essentially all expression of the 6 kb proximal enhancer/promoter (DRR/PRR) of MyoD in adult fibres. We propose that modulation of MyoD positive feedback by electrical activity determines the set point of MyoD expression in innervated fibres through the DRR/PRR element.
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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".