Coordinated epigenetic regulation of Engrailed-1 by the chromatin remodelers Smarca1 and Smarca5 mediates cerebellar morphogenesis
Why this work is in the frame
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Bibliographic record
Abstract
Background Morphological patterning of the cerebellum requires precise changes in Engrailed homeotic gene expression yet the mechanisms controlling this process remain elusive. Here, we show that the Iswi chromatin remodeling proteins, Smarca5 and Smarca1, are required for the dynamic regulation of Engrailed-1 (En1). Conditional Smarca5-null mice display abnormal cerebellar foliation, ataxia-like symptoms and young mortality. Postnatal granule neuron progenitor expansion and Purkinje cell (PC) development are compromised and attributed to loss of En1 expression. Mutants survive to early adulthood via upregulation of Smarca1 and restoration of En1 expression in PCs, while ablation of both Iswi genes results in lethality at birth. During late cerebellar development, we observe co-binding of the Iswi proteins at the En1 locus and an altered H2AZ/ H3.3 chromatin profile that accompanies changes in En1 expression.
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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 | 0.001 | 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