1α,25-Dihydroxycholecalciferol activates binding of CREB to a CRE site in the<i>CD14</i>promoter and drives promoter activity in a phosphatidylinositol-3 kinase-dependent manner
Bibliographic record
Abstract
1,25-dihydroxycholecalciferol, also known as 1alpha,25-dihydroxyvitamin D3 or calcitriol, regulates the differentiation and functional properties of mononuclear phagocytes. Many of these effects involve nongenomic signaling pathways, which are not fully understood. Activation of CD14 expression, a monocyte differentiation marker and coreceptor with TLR-2 for bacterial LPS, by calcitriol was shown previously to be PI-3K-dependent [1]; however, the mechanism of gene activation remained undefined. Using a transcription factor-binding array screen coupled with EMSA, we found evidence for PI-3K-dependent activation of CREB in THP-1 cells incubated with calcitriol. Furthermore, analysis of the proximal promoter of human CD14 identified regions that contained up to seven sequences, which showed significant similarity to a canonical CRE sequence, 5'-TGACGTCA-3'. Treatment of THP-1 cells with calcitriol activated CREB binding to one of these regions at Positions -37 to -55, relative to the transcription start site in a PI-3K-dependent manner. This 19-mer region also became transcriptionally active in a reporter assay in response to calcitriol, again dependent on PI-3K. Mutation of the CRE within the 19-mer abolished this activity. Taken together, these results show that calcitriol signaling, leading to activation of the CD14 promoter, involves CREB activation downstream of PI-3K.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".