Role of histone chaperone Nucleophosmin‐mediated transcriptional regulation in oral tumorigenesis
Bibliographic record
Abstract
Histone chaperones regulate the histone traffic in the cell and are involved in different cellular processes including transcription regulation. Nucleophosmin (NPM1), a histone chaperone, enhances acetylation‐dependent chromatin transcription. Acetylation of NPM1 by lysine acetyltransferase (KAT) p300 further enhances its histone chaperone activity and transcription activation potential. Moreover, the acetylated pool of NPM1 (AcNPM1) colocalizes with RNA Polymerase II foci in the nucleus, indicating its role in transcription. NPM1 is also a potent inducer of autoacetylation of p300 thereby enhancing its KAT activity. In the context of cancers, NPM1 is overexpressed in several solid tumors including oral squamous cell carcinoma and regulates genes implicated in oral cancer. AcNPM1 levels are also elevated with increasing grades of oral cancer. However, the precise role of AcNPM1 and the mechanism of transcription regulation by NPM1 are unclear. We performed chromatin immunoprecipitation followed by sequencing (ChIP‐seq) to identify the genome‐wide localization of AcNPM1 on chromatin. Interestingly we find that AcNPM1 is enriched on promoters of genes that are co‐occupied by RNA Polymerase II and other histone modifications related to active transcription. RNA‐sequencing after NPM1 knockdown in an oral cancer cell line revealed that NPM1 regulates the expression of genes involved in oral tumorigenesis. Inducible knockdown of NPM1 in an orthotopic mouse model also validates our finding that NPM1 indeed is involved in oral cancer manifestation. These results provide insights into the gene network regulated by NPM1 and AcNPM1 and the possible role of its overexpression and hyperacetylation in oral cancer. In the same context, the underlying mechanisms of transcriptional activation by NPM1/AcNPM1 and the role of NPM1 in the process of tumorigenesis are also currently under investigation. Support or Funding Information Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Sir JC Bose Fellowship, Department of Science and Technology (DST), India (Grant No. SR/S2/JCB‐28/2010), Department of Biotechnology (DBT), India (Programme Support on ‘Chromatin and Disease’, Grant No. BT/01/CEIB/10/III/01 and Virtual National Oral Cancer Institute, Grant No. BT/PR17576/MED/30/1690/2016) 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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".