BRG1 (Brahma-Related Gene 1) Promotes Endothelial <i>Mrtf</i> Transcription to Establish Embryonic Capillary Integrity
Bibliographic record
Abstract
Objective— The chromatin remodeling enzyme BRG1 (brahma-related gene 1) transcriptionally regulates target genes important for early blood vessel development and primitive hematopoiesis. However, because Brg1 deletion in vascular progenitor cells results in lethal anemia by embryonic day 10.5 (E10.5), roles for BRG1 in embryonic vascular development after midgestation are unknown. In this study, we sought to determine whether endothelial cell BRG1 regulates genes important for vascular development or maintenance later in embryonic development. Approach and Results— Using mice with temporally inducible deletion of endothelial BRG1 ( Brg1 fl/fl ;Cdh5(PAC)-Cre ERT2 ), we found that Brg1 excision between E9.5 and 11.5 results in capillary dilation and lethal hemorrhage by E14.5. This phenotype strongly resembles that seen when the SRF (serum response factor) transcription factor is deleted from embryonic endothelial cells. Although expression of Srf and several of its known endothelial cell target genes are downregulated in BRG1-depleted endothelial cells, we did not detect binding of BRG1 at these gene promoters, indicating that they are not direct BRG1 target genes. Instead, we found that BRG1 binds to the promoters of the SRF cofactors Mrtfa and Mrtfb (myocardin-related transcription factors A and B) in endothelial cells, and these genes are downregulated in Brg1 -deficient endothelial cells. Conclusions— BRG1 promotes transcription of endothelial Mrtfa and Mrtfb , which elevates expression of SRF and SRF target genes that establish embryonic capillary integrity. These data highlight a new and temporally specific role for BRG1 in embryonic vasculature and provide novel information about epigenetic regulation of Mrtf expression and SRF signaling in developing blood vessels.
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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) | 0.000 | 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 | 0.001 |
| 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".