Activating transcription factor 2 controls Bcl‐2 promoter activity in growth plate chondrocytes
Bibliographic record
Abstract
Activating transcription factor 2 (ATF-2) is expressed ubiquitously in mammals. Mice deficient in ATF-2 (ATF-2 m/m) are slightly smaller than their normal littermates at birth. Approximately 50% of mice born mutant in both alleles die within the first month. Those that survive develop a hypochondroplasia-like dwarfism, characterized by shortened growth plates and kyphosis. Expression of ATF-2 within the growth plate is limited to the resting and proliferating zones. We have previously shown that ATF-2 targets the cyclic AMP response element (CRE) in the promoters of cyclin A and cyclin D1 in growth plate chondrocytes to activate their expression. Here, we demonstrate that Bcl-2, a cell death inhibitor that regulates apoptosis, is expressed within the growth plate in proliferative and prehypertrophic chondrocytes. However, Bcl-2 expression declines in hypertrophic chondrocytes. The Bcl-2 promoter contains a CRE at -1,552 bp upstream of the translation start. Mutations within this CRE cause reduced Bcl-2 promoter activity. We show here that the absence of ATF-2 in growth plate chondrocytes corresponds to a decline in Bcl-2 promoter activity, as well as a reduction in Bcl-2 protein levels. In addition, we show that ATF-2 as well as CREB, a transcription factor that can heterodimerize with ATF-2, bind to the CRE within the Bcl-2 promoter. These data identify the Bcl-2 gene as a novel target of ATF-2 and CREB in growth plate chondrocytes.
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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 | 0.000 |
| 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".