Epigenetic control of RGS5 expression following femoral artery injury in mice
Bibliographic record
Abstract
RGS5 is involved in blood pressure regulation and tumor vascularization. Its expression is dynamic varying with age and disease, however, the specific pathways of regulation are unknown. Thus, the objective of this study is to identify the key modulators that regulate RGS5 expression. To assess the activity of the RGS5 promoter, which like other VSMC genes contains degenerate CArG boxes [CC(A/T) 6 GG], we generated a construct with luciferase under the control of the RGS5 promoter. This construct is 3‐fold more active in the presence of myocardin than with YFP control. Previous work in mouse carotid arteries show that degenerate CArGs are important in the post‐injury down‐regulation of several genes. In a model of femoral artery injury, we show that RGS5 expression decreases and remains so for up to 4 weeks. To understand pathways involved in this loss of expression, we looked at possible epigenetic changes. Using pyro‐sequencing and clonal analysis, we show that there is hypermethylation at 3 CpG sites in injured arteries compared to control. Interestingly, one site is within a degenerate CArG box suggesting that methylation could impede SRF binding and transcription activation. Thus, DNA methylation at sites important for promoter activity can be an effective way to silence RGS5 expression. This work was supported by the Canadian Institute of Health Research and the Heart and Stroke Foundation of Ontario.
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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 | 0.001 | 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".