A Positive Regulatory Domain in CCAAT/Enhancer Binding Protein β (C/EBPβ) Is Required for the Glucocorticoid-Mediated Displacement of Histone Deacetylase 1 (HDAC1) from the C/ebpα Promoter and Maximum Adipogenesis
Bibliographic record
Abstract
Glucocorticoids promote adipogenesis and contribute to the metabolic syndrome through a number of mechanisms. One of the effectors of glucocorticoid action is the CCAAT/enhancer binding protein β (C/EBPβ). C/EBPβ is a basic leucine-zipper transcription factor involved in diverse processes including differentiation, cellular proliferation, and inflammation. C/EBPβ transcriptional activity is regulated, in part, by its acetylation profile resulting from its dynamic interaction with either acetylases general control nonrepressed protein 5/p300/CBP associated factor (GCN5/PCAF) or deacetylase complexes (mSin3A/histone deacetylase 1 [HDAC1]). Glucocorticoid treatment of preadipocytes promotes C/EBPβ acetylation, leading to mSin3A/HDAC1 dissociation from C/EBPβ and resulting in C/ebpα promoter activation at the onset of adipogenesis, thus increasing the differentiation rate. We recently showed that the regulatory domain 1 (RD1) of C/EBPβ contains four residues (153-156) required for its interaction with HDAC1, therefore supporting RD1 proposed inhibitory role. In an attempt to further elucidate the intrinsic regulatory property of RD1, we sought to characterize the regulatory potential of the N terminus region of RD1 (residues 141-149). In this study, we show that C/EBPβΔ141-149 transcriptional activity was compromised on the C/ebpα, but not on the Pparγ, promoter. Additionally, the ability of C/EBPβΔ141-149 to induce adipogenesis in NIH 3T3 cells was compromised when compared with C/EBPβwt owing to a delayed expression of C/ebpα at the onset of differentiation. Furthermore, the data suggest that the reduced expression of C/ebpα in cells expressing C/EBPβΔ141-149 was due to a persistent recruitment of HDAC1 to the C/ebpα promoter after glucocorticoid treatment. Together, these results suggest that amino acids 141-149 of C/EBPβ act as a positive regulatory domain required for maximum transcriptional activity.
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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) | 0.002 | 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".