PACAP‐regulated phenylethanolamine<i>N</i>‐methyltransferase gene expression
Bibliographic record
Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP) induces the proximal -893 bp of rat phenylethanolamine N-methyltransferase (PNMT) gene promoter in PC12 cells via PACAP type I receptors. Deletion mutation analysis suggested that the initial -392 bp of promoter, containing early growth response protein (Egr-1), specificity protein 1 (Sp1) and activator protein 2 (AP-2) binding sites (-165, -168 and -103 bp, respectively), was sufficient for PACAP activation. Egr-1 and AP-2 involvement was supported by PACAP induction of their mRNA and protein. Mutation of the Egr-1, Sp1 and AP-2 elements showed that the Egr-1 site was essential for PACAP stimulation. Mutation of the -103 bp AP-2 site partially reduced PACAP activation of the promoter. Mutation of two upstream AP-2 sites at -573 and -650 bp, separately or in tandem, also prevented promoter induction by PACAP. siRNA knock-down of Egr-1 and AP-2 suppressed promoter activation for the -893 bp construct. Egr-1 siRNA knock-down also eliminated the residual activation observed for the -103 bp AP-2 mutant construct, suggesting that Egr-1 and AP-2 through respective -165 and -650/-573/-103 bp sites cooperatively stimulate the promoter. PACAP responses appear orchestrated through cAMP-protein kinase A and phospholipase C signaling as MDL12,330A, H89 and U73122, respectively, inhibited promoter induction by PACAP and reduced PACAP-stimulation of Egr-1, AP-2 and PNMT mRNA and protein and Egr-1 and AP-2 protein/DNA complex formation. Findings are the first to show that PACAP stimulates PNMT promoter-driven gene expression via PACAP type I receptors and cAMP-protein kinase A and phospholipase C signaling, recruiting Egr-1 and AP-2 as cooperative regulators, and the first to associate the transcription factor AP-2 to PACAP-mediated gene induction.
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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) | 0.001 | 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".