Identification of GAS‐dependent interferon‐sensitive target genes whose transcription is STAT2‐dependent but ISGF3‐independent
Bibliographic record
Abstract
Signal transducer and activator of transcription 2 (STAT2) is best known as a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes. However, STAT2 is also involved in DNA binding in non-ISGF3 transcriptional complexes. We used a DNA microarray to survey the expression of genes regulated by IFN-inducible, STAT2-dependent DNA binding, and compared the cDNAs of IFN-treated cells overexpressing intact STAT2 to those of IFN-treated cells overexpressing mutated STAT2 lacking the DNA binding domain. The IFN-inducible expression of genes known to be regulated by ISGF3 was similar in both cases. However, a subset of IFN-inducible genes was identified whose expression was decreased in cells expressing the mutated STAT2. Importantly, these genes all contained gamma-activated sequence (GAS)-like elements in their 5' flanking sequences. Our data reveal the existence of a collection of GAS-regulated target genes whose expression is IFN-inducible and independent of ISGF3 but highly dependent on the STAT2 DNA binding domain. This report is the first analysis of the contribution of the STAT2 DNA binding domain to IFN responses on a global basis, and shows that STAT2 is required for the IFN-inducible activation of the full spectrum of GAS target genes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
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 teacher head, 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".