Mapping chromatin contacts in the human MYB locus
Bibliographic record
Abstract
The MYB gene encodes for a transcription factor that has an important role in regulating normal hematopoietic proliferation and differentiation.Aberrant expression of this gene is strongly associated with leukemogenesis in humans.To better understand how this gene is regulated in leukemia, we studied the chromatin organization of the gene locus in the human acute myeloid leukemia cell line THP-1, and, in human embryona carcinoma cell line NT2D1.We observed a similar chromatin contact pattern between CTCF binding regions previously identified in mouse.Interestingly, the upstream region from the MYB gene forms a strong chromatin contact to its gene body rather than the promoter.In this upstream region, MLL binding is observed.Knockdown of MLL protein caused the repression of MYB gene expression and reduction of H3K4me1 marks surrounding the MYB gene locus.Our data suggest that the MLL protein is amongst the factors maintaining high-level MYB gene expression and its epigenetics states via chromatin organization.Based on our data, we propose that cancer cells mediate chromatin contacts around the MYB gene locus leading to its dysregulation.We observe no change in chromatin organization after induced cell differentiation despite the downregulation of MYB gene.For MLL associated leukemogenesis, our data brings new insight to the regulation of abnormal gene expression based on the context of chromatin organization.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".