FOXP3 expression depends on cell-type-specific cis-regulatory elements and transcription factor circuitry
Bibliographic record
Abstract
FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Treg cells). Although mice exclusively express FOXP3 in Treg cells, stimulated conventional CD4 + T cells (Tconv cells) also transiently express FOXP3 in humans. Mechanisms governing these distinct expression patterns need elucidation. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Treg and Tconv cells to identify cis -regulatory elements (CREs) and trans -regulators of FOXP3. Tconv cell FOXP3 expression depended on a subset of Treg cell CREs, as well as Tconv-cell-selective positive (NS+) and negative (NS−) CREs. Combinatorial silencing of Tconv cell CREs revealed their epistatic logic. These CREs are occupied and regulated by TFs that we identified as FOXP3 regulators. Finally, mutagenesis of murine NS− CRE revealed its essentiality for restricting FOXP3 expression to Treg cells. We map CRE and TF circuitry to reveal distinct cell- and species-specific regulation of FOXP3 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".