Sirt2 is a novel in vivo downstream target of Nkx2.2 and enhances oligodendroglial cell differentiation
Bibliographic record
Abstract
Although Sirt2 is primarily expressed in oligodendrocytes of the central nervous system, its role in oligodendroglial lineage differentiation is not fully understood. Our findings demonstrate that the transcription factor Nkx2.2 binds to the Sirt2 promoter via histone deacetylase 1 (HDAC-1), the binding site for Nkx2.2 maps close to the start codon of the Sirt2 gene, and Nkx2.2 negatively regulates Sirt2 expression in CG4 cells, an oligodendroglial precursor cell line. HDAC-1 knock-down not only significantly attenuates the binding capacity of Nkx2.2 to the Sirt2 promoter but also releases repression of Sirt2 expression by Nkx2.2. Nkx2.2 over-expression down-regulates Sirt2 expression and delays differentiation of CG4 cells; in contrast, up-regulation of Sirt2 does not impact Nkx2.2 expression level. Sirt2 knock-down via RNAi or inhibition of Sirt2 by sirtinol, a Sirt2 activity inhibitor, blocks CG4 cell differentiation. Over-expression of Sirt2 facilitates CG4 cell differentiation at both molecular and cellular levels, enhancing expression of myelin basic protein and facilitating the growth of cell processes. We have conclusively demonstrated that Sirt2 enhances CG4 oligodendroglial differentiation and report a novel mechanism through which Nkx2.2 represses CG4 oligodendroglial differentiation via Sirt2.
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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) | 0.003 | 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".