Transcriptional cooperation between NF-κB p50 and CCAAT/enhancer binding protein β regulates Nur77 transcription in Leydig cells
Bibliographic record
Abstract
Expression of steroidogenic enzyme-encoding genes in testicular Leydig cells is complex and involves several transcription factors including the orphan nuclear receptor NUR77 (NR4A1) and the bZIP factor CCAAT/enhancer binding protein beta (EBPbeta). How these transcription factors are integrated into a functional network, however, remains to be fully understood. Here, we report that the transcription factor C/EBPbeta can activate the Nur77 promoter as revealed by transient transfections in MA-10 Leydig cells. Through 5' progressive deletions and site-directed mutagenesis, the C/EBPbeta-mediated activation of the Nur77 promoter was found to be dependent on a novel species-conserved C/EBP element located at -110 bp. We also demonstrate using electromobility shift assay that C/EBPbeta specifically binds to this element. Furthermore, we report a functional cooperation between C/EBPbeta and the p50 subunit of NF-kappaB that involves a previously uncharacterized kappaB element located at -18 bp. Promoter analysis revealed that either the C/EBP or the kappaB element was sufficient to sustain the C/EBPbeta-p50 cooperation thus suggesting that both factors physically interact. Altogether, our results provide new data regarding Nur77 transcription in testicular Leydig cells in addition to providing new insights into the interplay between transcription factors involved in Leydig cell gene expression and function.
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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".