CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice
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Bibliographic record
Abstract
Haploinsufficiency for CHD7, an ATP-dependent nucleosome remodeling factor, is the leading cause of CHARGE syndrome. While congenital heart defects (CHDs) are major clinical features of CHARGE syndrome, affecting >75% of patients, it remains unclear whether CHD7 can directly regulate cardiogenic genes in embryos. Our complementary yeast two-hybrid and biochemical assays reveal that CHD7 is a novel interaction partner of canonical BMP signaling pathway nuclear mediators, SMAD1/5/8, in the embryonic heart. Moreover, CHD7 associates in a BMP-dependent manner with the enhancers of a critical cardiac transcription factor, Nkx2.5, that contain functional SMAD1-binding elements. Both the active epigenetic signature of Nkx2.5 regulatory elements and its proper expression in cardiomyocytes require CHD7. Finally, inactivation of Chd7 in mice impairs multiple BMP signaling-regulated cardiogenic processes. Our results thus support the model that CHD7 is recruited by SMAD1/5/8 to the enhancers of BMP-targeted cardiogenic genes to epigenetically regulate their expression. Impaired BMP activities in embryonic hearts may thus have a major contribution to CHDs in CHARGE syndrome.
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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