Expression of a Human β-Globin Transgene in Mice with the CACC Motif and Upstream Sequences Deleted from the Promoter Still Depends on Erythroid Krüppel-like Factor
Bibliographic record
Abstract
Mice in which the erythroid Krüppel-like Factor (EKLF) gene is inactivated die in fetal life due to down-regulation of the beta-globin gene. Results have suggested that EKLF functions through the proximal CACC motif of the beta-globin promoter. For example, natural mutations of this element that fail to bind EKLF give reduced gene expression and the ability of EKLF to activate reporter genes in co-transfection assays is dependent on an intact CACC. Here, removal of the CACC motif and upstream promoter sequences from the beta-globin gene resulted in reduced expression in transgenic mice. However, breeding onto an EKLF-/- background demonstrated that a CACC-less beta-globin transgene remains highly dependent on EKLF. Hence, although the beta-globin gene partly depends on the proximal CACC motif for expression, it is unlikely that the major mechanism of gene activation by EKLF is through this element. We also show that a lacZ reporter gene linked to the beta-globin promoter, with or without the CACC box present, is actually expressed higher in EKLF-/- fetuses than in wild type animals, suggesting that EKLF may be able to act as an inhibitor of transcription with certain transgene configurations.
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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 | 0.001 |
| 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".