Immediate-Early and Delayed Primary Response Genes Are Distinct in Function and Genomic Architecture
Bibliographic record
Abstract
The transcriptional program induced by growth factor stimulation is classically described in two stages as follows: the rapid protein synthesis-independent induction of immediate-early genes, followed by the subsequent protein synthesis-dependent induction of secondary response genes. In this study, we obtained a comprehensive view of this transcriptional program. As expected, we identified both rapid and delayed gene inductions. Surprisingly, however, a large fraction of genes induced with delayed kinetics did not require protein synthesis and therefore represented delayed primary rather than secondary response genes. Of 133 genes induced within 4 h of growth factor stimulation, 49 (37%) were immediate-early genes, 58 (44%) were delayed primary response genes, and 26 (19%) were secondary response genes. Comparison of immediate-early and delayed primary response genes revealed functional and regulatory differences. Whereas many immediate-early genes encoded transcription factors, transcriptional regulators were not prevalent among the delayed primary response genes. The lag in induction of delayed primary response compared with immediate-early mRNAs was because of delays in both transcription initiation and subsequent stages of elongation and processing. Consistent with increased abundance of RNA polymerase II at their promoters, immediate-early genes were characterized by over-representation of transcription factor binding sites and high affinity TATA boxes. Immediate-early genes also had short primary transcripts with few exons, whereas delayed primary response genes more closely resembled other genes in the genome. These findings suggest that genomic features of immediate-early genes, in contrast to the delayed primary response genes, are selected for rapid induction, consistent with their regulatory functions.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".