Cardiac restricted overexpression of E2F6 alters cell cycle dynamics and results in dilated cardiomyopathy in mice
Bibliographic record
Abstract
The E2F transcription factors play a critical role in cell cycle control and developing myocardium. Cardiomyocytes undergo permanent cell cycle arrest shortly after birth and we investigated the role of E2F6, a repressor of E2F‐responsive genes, by generating transgenic (Tg) mice with cardiac‐specific expression of E2F6 driven by the alpha‐myosin heavy chain promoter. Three independent Tg lines with different levels of E2F6 (~3‐, 6‐ and 9‐fold vs wild type) were established, which showed mortality and CHF symptoms in young adults, with increasing severity correlating with E2F6 levels. Echocardiography showed progressive LV dilation and decreasing ejection fractions in Tg mice. E2F6 targeted the nucleus with a profound reduction in phospho‐histone H3 staining but no changes in apoptosis in 4‐day‐old Tg hearts. Increases in the G1/S phase markers cyclin D3, cdk4, p‐Rb were noted while the G2/M marker p‐cdc2 did not change in Tg hearts. Heterochromatin formation was attenuated in Tg hearts, as reflected by reduced methylated histone H3, and histone deacetylase 4 protein. These data suggest that regulated expression of E2F6 is critical for normal cardiac development and function, since overexpression alters chromatin remodeling and cell cycle dynamics, resulting in dilated cardiomyopathy. (Supported by CIHR and HSFO).
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".