The H3K27 acetyltransferase p300 is dispensable for thermogenic adipose tissue formation and function
Bibliographic record
Abstract
Abstract Brown adipose tissue (BAT) is specialized for thermogenesis because it contains uncoupling protein (UCP)-1. BAT is also an endocrine organ, producing many signalling molecules important for regulating the metabolism of peripheral organs. Mounting evidence suggest that histone modifying enzymes are integral for the development, tissue maintenance, and postnatal functioning of brown and beige adipocytes. p300 and its functional homologue CREB-binding protein (CBP) are histone acetyltransferases that form the transcriptionally activating histone 3 acetyl-lysine 27 (H3K27ac) mark. Using Ucp1- Cre, we examined the requirement of p300 activity specifically within thermogenic adipocytes. We hypothesized that loss of p300 activity would impair gene programming integral for BAT development/function, rendering knockouts susceptible to metabolic dysfunction and unable to form beige adipocytes. Despite successful knockdown, brown fat was completely unaffected by p300 deletion. As such, knockout mice showed a comparable metabolic profile to littermate controls in response to diet-induced obesity. Furthermore, de novo beige adipogenesis within subcutaneous fat by a β 3 adrenergic agonist remained intact in knockout mice. Although p300 and CBP have non-overlapping roles in other tissues, our results indicate p300 HAT activity is dispensable within thermogenic fats, likely due to functional compensation by CBP.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".