Characterization of a Repressor Element and a Juxtaposed Tissue-restricted Activator Element Located on the Distal neu Gene Promoter
Bibliographic record
Abstract
The proto-oncogene neu (HER2 or c-erbB2) is overexpressed with or without gene amplification in 20-30% of breast cancers. In patients, neu amplification or overexpression in breast and ovarian cancer correlates with poor prognosis and tumor resistance to chemotherapy. neu-induced transformation can be reversed by the suppression of neu gene transcription. To further understand how neu gene transcription is regulated and to identify a possible transcriptional repressor(s) of neu, we identified a negative regulatory element known previously to be located within a 1-kilobase (kb) DNA fragment of an unknown sequence, upstream of the proximal neu gene promoter. One of several DNA fragments subcloned from this region suppressed transcriptional activity of the proximal neu gene promoter. Sequencing of the 1-kb fragment confirmed the location of the repressor element to be between an AluI and a RsaI sites, around 1.4 kb upstream to the translation start site. Various deletions were introduced into the AluI-RsaI fragment and subcloned into both the native neu promoter and a heterologous thymidine kinase promoter. Subsequent transfections and reporter gene assays in cell lines of various tissues of origin confirmed and narrowed the repressor activity to a 120-base pair NlaIV-MslI fragment located between -1385 and -1266. Importantly, specific protein binding activity to this element could be detected with nuclear extracts isolated from these cell lines. In contrast, a 28-base pair MslI-RsaI fragment (-1265 to -1238), located immediately 3' of the putative repressor element, was found to form protein-DNA complexes with only nuclear extracts isolated from a colon carcinoma cell line. This specific protein binding activity correlated with a previously unknown transcriptional stimulatory activity only in this cell line.
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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".