Local G-quadruplexes are not a major determinant of altered gene expression in BLM-deficient cells
Bibliographic record
Abstract
Abstract Mutations in the Blm gene can cause Bloom Syndrome, a genetic disorder characterized by genome instability and cancer predisposition. Blm encodes a helicase which was reported to resolve G-quadruplex DNA structures in vitro . The G-quadruplex resolving activity of the BLM helicase has been previously implicated in altering gene expression. However, the exact mechanisms of how G-quadruplex structures may affect gene expression remain to be elucidated. We employed experimentally defined G-quadruplex forming DNA sequences and generated transcriptomes for several Bloom Syndrome patient-derived cell lines and BLM-deficient mouse embryonic stem cells to further investigate the effect of G-quadruplexes on gene expression. Our results do not support the previous findings that G-quadruplexes located within a gene play a major role in altering its expression in BLM-deficient cells. We found concerted large-scale changes in transcript abundance, splicing, nucleosome occupancy, and phasing, that cannot be linked to the local presence of G-quadruplex sequences in either gene bodies or promotors. The investigation of genomic features associated with large-scale differences in nucleosome density highlights the rDNA locus and active enhancers as the most strongly affected regions. We hypothesize that global changes in chromatin structure rather than local G4s might mediate the transcriptome changes in the absence of BLM.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".