Characterization of a negative transcriptional element in the BRCA1 promoter
Bibliographic record
Abstract
INTRODUCTION: Decreased transcription of the BRCA1 gene has previously been observed to occur in sporadic breast tumours, making elucidation of the mechanisms regulating the expression of this gene important for our understanding of the etiology of the disease. METHODS: Transcriptional elements involved in the regulation of the BRCA1 promoter were analysed by co-transfection experiments into the human MCF-7 and T-47D breast cancer cell lines. RESULTS: We have identified a repressor element, referred to as the UP site, within the proximal BRCA1 promoter whose inactivation results in increased promoter activity. An E2F recognition element, previously suggested to mediate repression via E2F-6, is adjacent to the UP site and its inactivation also leads to increased BRCA1 expression. These two elements appear to form a composite repressor element whose combined effect is additive. The UP element is composed of two sequences, one of which binds the ubiquitously expressed ets family transcription factor GABP alpha/beta. This site is distinct from a previously identified GABP alpha/beta site, the RIBS element, though the RIBS site appears to be necessary for derepression of the promoter via mutations in the UP site. Knockdown of GABP alpha using an shRNA vector confirms that this protein is important for the function of both the RIBS and UP sites. CONCLUSION: The identification of a repressor element in the BRCA1 promoter brings a new level of complexity to the regulation of BRCA1 expression. The elements characterized here may play a normal role in the integration of a variety of signals, including two different growth related pathways, and it is possible that loss of the ability to derepress the BRCA1 promoter during critical periods may contribute to breast transformation.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".