The myeloid lineage‐determining transcription factor PU.1 induces enhancer‐promoter looping that promotes IL‐1β enhancer and messenger RNA production in non‐myeloid melanoma cells
Bibliographic record
Abstract
The DNA‐binding protein purine rich (PU.1) is a lineage determining transcription factor required for development of myeloid cells such as monocytes/macrophages. PU.1 is regarded as a pioneering transcription factor for macrophage differentiation due to its ability to bind “closed” genomic sites and initiate/maintain “open” chromatin state in macrophage‐restricted response genes. To date, however, precise mechanism of PU.1 in remodeling chromatin is yet to be elucidated. The non‐myeloid melanoma B16.BL6 cells response to the bacterial cell wall component lipopolysaccharide (LPS) and activate the transcription factor NF‐κB, but do not produce cytokines. Ectopic expression of PU.1 rendered these cells express the cytokine interleukin 1‐β (IL1b) in response to LPS. PU.1 induced chromatin remodeling that caused interaction between the IL1b promoter and enhancer (located ~10 kb upstream of the IL1b transcription start site) in non‐activated cells; upon activation, PU.1 recruited NF‐κB to these genomic regions. The N‐terminal domain (1–30) of PU.1 was important for both promoter‐enhancer looping and IL1b eRNA/mRNA production; whereas, the acidic and glutamine rich domains (33–100) were required for eRNA/mRNA production but dispensable for the DNA looping. eRNA production and histone acetylation were required for NF‐κB recruitment and IL1b mRNA expression, but not for the DNA looping. Altogether, this study indicates that PU.1 induces enhancer‐promoter looping that sequentially allows activation‐dependent histone acetylation, recruitment of NF‐κB and production of enhancer RNAs, all of which are required for an optimal IL1b production. Support or Funding Information The Natural Sciences and Engineering Research Council of Canada ‐ Discovery Grant (RGPIN‐2018‐05514) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.002 | 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".