Impact of somatic <i>XIST</i> deletions on ongoing XIST expression and inactive X silencing and heterochromatin
Bibliographic record
Abstract
The long non-coding RNA XIST is critical for establishing X-chromosome inactivation early in development. XIST remains expressed from the inactive X throughout female life; yet in somatic cells silencing of most genes continues in the absence of XIST. As changes in XIST expression are observed in cancers and aging we sought to examine the impact of complete or partial XIST loss on gene expression and chromatin structure in the hTERT RPE-1 cell line. XIST regulatory elements lie within the gene, with ongoing expression dependent on the A repeat region. Upon loss of XIST expression there was up-regulation of a subset of X-linked genes, with escape genes showing an average 20% increase in expression. Near full Xi-expression was found for MED14 and USP9X upon XIST loss, with partial up-regulation observed with the reduced XIST expression caused by removal of the F-repeat containing region or XIST delocalization following deletion of the E repeat region. Comparison with other studies of XIST loss in human cell lines revealed recurrent impact on escapees, while autosomal genes demonstrated no consistent XIST-dependencies. Loss of XIST in hTERT RPE-1 resulted in loss of H3K27me3 and H2AK119ub; however, independent inhibition of these pathways failed to upregulate MED14 and USP9X. In contrast, reduction of H3K9me3 caused partial reactivation of USP9X but not MED14, thus implicating a combinatorial action of silencing pathways in X-chromosome inactivation. Our work, in agreement with previous studies, reveals that in somatic cells XIST expression and localization suppresses the expression of escape genes.
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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 | 0.000 |
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 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".