The p15ink4B tumor suppressor is a direct target for the ZNF217 oncoprotein
Bibliographic record
Abstract
2779 ZNF217 is a kruppel-like transcription factor and candidate oncogene that is amplified and overexpressed in multiple cancer cell lines and tumours and recent evidence indicates that ZNF217 overproduction results in abnormal cell growth. ZNF217 is a major constituent of a transcriptional complex containing chromatin-modifying activities known to promote transcriptional repression and include the repressor CoREST, the histone deacetylase 2 (HDAC2) that catalyzes removal of acetyl groups from conserved lysines on histones, lysine demethylase I (LSD1) which removes mono- or di-methyl groups on lysine 4 of histone H3 (H3K4), and the C terminal binding protein (CtBP). In this study we have combined (1) genome wide expression profiling of cancer cells in which ZNF217 has been downregulated using siRNA and (2) chromatin immunoprecipitation (ChIP) in conjunction with DNA selection and ligation (ChIP-DSL), to identify genes directly regulated by ZNF217 in MCF7 breast cancer cells. Our results indicate that the tumour suppressor p15ink4b is a direct target of the ZNF217 complex. Furthermore ZNF217, CoREST and LSD1 are all highly enriched within a region of the promoter that is essential for activation of p15INK4B. To determine whether silencing of p15INK4B is dependent on the ZNF217 complex, we transfected MCF-7 cells with siRNA targeting either ZNF217 or LSD1 and ink4b expression was monitored by realtime PCR or western blotting. A dramatic increase in p15INK4B expression was observed providing strong evidence that the ZNF217 complex is a key repressor of the p15INK4B gene in MCF7 cells. Importantly, the identification of the ink4b gene as a direct target for the ZNF217 corepressor complex represents a potentially novel link between amplification of ZNF217 and the loss of TGFβ responsiveness in breast cancer.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".