Global Profiling of c-Jun and JunB transcription factor binding sites in an ALK+ ALCL cell line
Bibliographic record
Abstract
Abstract Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma which features translocations or inversion involving the ALK tyrosine kinase gene, and results in oncogenic fusion proteins (e.g. NPM-ALK). The elevated expression and/or activation of activator protein-1 (AP-1) transcription factors, c-Jun and JunB, is another molecular feature of ALK+ ALCL. c-Jun/JunB transcriptional targets are important in the pathobiology of this lymphoma, and several are also therapeutic targets. To better understand c-Jun/JunB function in ALK+ ALCL, we performed chromatin immunoprecipitation–sequencing experiments in the Karpas 299 ALK+ ALCL cell line to comprehensively identify sites bound by these transcription factors. We identified 13,083 c-Jun and 40,369 JunB binding sites, and ∼60% of sites bound by c-Jun were shared with JunB. Many sites were associated with genes known or predicted to be important in the pathogenesis of ALK+ ALCL. Pathway enrichment analysis of genes associated with both c-Jun and JunB binding sites revealed a significant over-representation for pathways associated with cancer and cell signalling. Furthermore, we identified several c-Jun and JunB binding sites associated with the NIBAN2 / FAM129B gene. FAM129B is a PH domain-containing phosphoprotein that promotes proliferation in multiple cell types. However, while we found that FAM129B knock-down resulted in modest cell cycle alteration in most ALK+ ALCL cell lines, this did not appear to result in a significant proliferation defect. Finally, we found that inhibition of NPM-ALK and MEK/Erk signalling altered FAM129B electrophoretic mobility and decreased phosphorylation of FAM129B on serine residues known to be Erk phosphosites. In summary, this study is the first to globally profile sites bound by c-Jun/JunB in ALK+ ALCL. It reveals novel putative targets for these transcription factors in ALK+ ALCL, and identifies FAM129B as a novel phosphoprotein downstream of NPM-ALK signalling.
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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 | 0.001 | 0.001 |
| 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) | 0.001 | 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 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".