Abstract 2263 A repressive compartment silences subtelomeric chromatin in trypanosomes
Bibliographic record
Abstract
Chromatin compartmentalization is essential for the monogenic expression of variant surface glycoprotein (VSG) genes in African trypanosomes. Trypanosomes express one out of 2,500 VSG genes at a time from telomeric expression sites (ESs). VSGs form a homogenous surface coat essential for parasite evasion of host antibodies by antigenic variation. Trypanosomes periodically switch the VSG expressed by transcriptional switching among telomeric ESs or by VSG gene recombination. Most silent VSG genes are subtelomeric and silenced by mechanisms still not understood. We found that subtelomeric chromatin is organized within repressive compartments essential for silencing VSG genes. Chromatin capture (Pore-C) experiments showed significant enrichment in interactions of silent subtelomeres, whereas the actively transcribed subtelomeric VSG gene interacts with highly transcribed chromosome loci. Fluorescence in situ hybridization and microscopy analysis confirmed telomeric and subtelomeric chromatin compartmentalization. In vivo crosslinking and mass spectrometry interaction analysis of the phosphatidylinositol phosphate 5-phosphatase (PIP5Pase) protein, which regulates VSG gene silencing, revealed a network of interactions involved in compartment assembly and gene repression. Genetic mutations that affect PIP5Pase activity resulted in the reorganization of subtelomeric chromatin, followed by transcription of silent subtelomeric genes and the switching in VSG gene expression. The data indicate that subtelomeric chromatin assembles into repressive compartments that coordinates the repression of hundreds of VSG genes. The compartments are essential for coordinated expression of surface antigens during antigenic variation. This work was funded by Canadian Institutes of Health Research (IC); The Natural Sciences and Engineering Research Council of Canada (IC); Fonds de Recherche du Québec - Nature et Technologie (IC); Canada Foundation for Innovation (IC); and FRQNT-Ukraine postdoctoral fellowship (OK).
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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".