Chromatin-specific regulation of LEF-1–β-catenin transcription activation and inhibition in vitro
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Bibliographic record
Abstract
Transcriptional activation of Wnt/Wg-responsive genes requires the stabilization and nuclear accumulation of beta-catenin, a dedicated coactivator of LEF/TCF enhancer-binding proteins. Here we report that recombinant beta-catenin strongly enhances binding and transactivation by LEF-1 on chromatin templates in vitro. Interestingly, different LEF-1 isoforms vary in their ability to bind nucleosomal templates in the absence of beta-catenin, owing to N-terminal residues that repress binding to chromatin, but not nonchromatin, templates. Transcriptional activation in vitro requires both the armadillo (ARM) repeats and the C terminus of beta-catenin, whereas the phosphorylated N terminus is inhibitory to transcription. A fragment spanning the C terminus (CT) and ARM repeats 11 and 12 (CT-ARM), but not the CT alone, functions as a dominant negative inhibitor of LEF-1-beta-cat activity in vitro and can block ATP-dependent binding of the complex to chromatin. LEF-1-beta-cat transactivation in vitro was also repressed by inhibitor of beta-catenin and Tcf-4 (ICAT), a physiological inhibitor of Wnt/Wg signaling that interacts with ARM repeats 11 and 12, and by the nonsteroidal anti-inflammatory compound, sulindac. None of these transcription inhibitors (CT-ARM, ICAT, or sulindac) could disrupt the LEF-1-beta-cat complex after it was stably bound to chromatin. We conclude that the CT-ARM region of beta-catenin functions as a chromatin-specific activation domain, and that several inhibitors of the Wnt/Wg pathway directly modulate LEF-1-beta-cat activity on chromatin.
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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 it