Modelling transcriptional feedback loops: the role of Gro/TLE1 in Hes1 oscillations
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Bibliographic record
Abstract
The transcriptional repressor Hes1, a basic helix-loop-helix family protein, periodically changes its expression in the presomitic mesoderm. Its periodic pattern of expression is retained in a number of cultured murine cell lines. In this paper, we introduce an extended mathematical model for Hes1 oscillatory expression that includes regulation of Hes1 transcription by Drosophila Groucho (Gro) or its vertebrate counterpart, the transducine-like enhancer of split/Groucho-related gene product 1 (TLE1). Gro/TLE1 is a necessary corepressor required by a number of DNA-binding transcriptional repressors, including Hes1. Models of direct repression via Hes1 typically display an expression overshoot after transcription initiation which is not seen in the experimental data. However, numerical simulation and theoretical predictions of our model show that the cofactor Gro/TLE1 reduces the overshoot and is thus necessary for a rapid and finely tuned response of Hes1 to activation signals. Further, from detailed linear stability and numerical bifurcation analysis and simulations, we conclude that the cooperativity coefficient (h) for Hes1 self-repression should be large (i.e. h>or=4). Finally, we introduce the characteristic turnaround duration, and show that for our model the duration of the repression loop is between 40 and 60 min.
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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 | 0.001 |
| 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