Redundant and Synergistic Effect of Cdx-2 and Brn-4 on Regulating Proglucagon Gene Expression
Bibliographic record
Abstract
Cdx-2 and Brn-4 are recognized as transcriptional activators for the proglucagon gene. These two homeodomain (HD) proteins are able to interact with the correspondent motifs on the G1 enhancer element of proglucagon promoter, separated by only 8 bp. We have examined Brn-4 expression in proglucagon-producing cells, isolated hamster Brn-4 cDNA, and localized its activation domain. Ectopic expression of either Cdx-2 or Brn-4 in the pancreatic B cell line In111 provoked it to express proglucagon mRNA, whereas ectopically expressing both of them further stimulated proglucagon mRNA expression in this cell line. Furthermore, Brn-4 was found to synergize with Cdx-2 in activating proglucagon promoter, and the Brn-4 activation domain was not required for this synergistic activation. When the binding site for either Cdx-2 or Brn-4 was mutated, the synergistic activation by these two HD proteins was significantly attenuated, but not abolished. We propose that both cooperative DNA binding and mutual recruitment between Cdx-2 and Brn-4 are involved in this synergistic activation and have detected physical interaction between Cdx-2 and Brn-4 by glutathione-S-transferase-fusion protein pull-down assay. Our observations suggest that Cdx-2 and Brn-4, two HD proteins that belong to two different families, exert a synergistic and redundant effect on proglucagon gene expression.
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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) | 0.001 | 0.000 |
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".