Role of chromatin remodeling and spacing factor 1 in histone H2A ubiquitination mediated gene silencing
Bibliographic record
Abstract
Posttranslational modification of histones plays important regulatory roles in chromatin‐based nuclear processes. Histone H2A ubiquitination (H2Aub) is a predominate modification and has been primarily linked to gene silencing; however, the mechanism by which H2Aub achieves the gene silencing function remains unclear. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF (remodeling and spacing factor) complex, as a novel H2Aub binding protein which mediates the repressive function of H2Aub on gene expression. RSF1 preferentially associates with H2Aub‐enriched nucleosomes through a previously uncharacterized region designated as the ubiquitinated H2A binding (UAB) motif. RSF1 specifically interacts with H2Aub nucleosomes and the UAB motif is required for RSF1 to interact with H2Aub nucleosomes in vitro and in vivo . Genes regulated by RSF1 overlap significantly with genes regulated by RNF2 or Ring1B, the catalytic subunit of Polycomb repressive complex 1 (PRC1), in both human and mouse cells. Strikingly, virtually all overlapped genes show changes in the same direction. RSF1 binds to gene promoter regions, and over 85% of H2Aub enriched genes, including the classic PRC1‐target Hox genes, are co‐bound by RSF1. Reduction H2Aub levels by Ring1B knockout resulted in a significant reduction of RSF1 binding. RSF1 knockout did not affect RNF2/Ring1B or H2Aub levels but resulted in re‐expression of H2Aub target genes, accompanied by a reduction in the spacing and stability of H2Aub‐containing nucleosomes. Finally, the direct role of RSF1 in H2Aub‐mediated gene silencing was demonstrated by chromatin based in vitro transcription assay. Therefore, this study identifies RSF1 as a novel H2Aub binding protein and reveals that H2Aub represses gene expression by maintaining a regular spaced, stable nucleosome array at promoter regions through RSF1. Support or Funding Information Hengbin Wang is a Leukemia and Lymphoma Scholar.
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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) | 0.001 | 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".