Reviewer #2 (Public review): Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression
Bibliographic record
Abstract
Mammalian genomes are organized by multi-level folding, yet how this organization contributes to cell type-specific transcription remain unclear. We uncovered that the nuclear protein SATB1 establishes two-tiered chromatin organization, one through indirect binding and another by direct binding of base-unpairing regions (BURs), which are genomic elements with high unwinding propensities. Published ChIP-seq datasets show SATB1 binding to highly accessible chromatin at enhancers and CTCF sites, but not to BURs. By employing urea ChIP-seq, which retains only directly bound protein:DNA complexes, we found that BURs, but not CTCF sites, are direct SATB1 binding targets. SATB1-bound BUR interactions with accessible chromatin can cross multiple topologically associated domains (TADs) and SATB1 is required for these megabase-scale interactions linked to cell type-specific gene expression. BURs are mainly found within lamina associated domains (LADs) sequestered at the nuclear lamina, but also in inter-LADs, and SATB1 binds a subset of BURs depending on cell type. Notably, despite the mutually exclusive SATB1-binding profiles uncovered by the two ChIP-seq methods, we found most peaks in both profiles are real and require SATB1. Together, we propose that SATB1 has functionally distinct modes of chromatin interaction by directly binding BURs to form a chromatin scaffold to which it indirectly tethers open chromatin. Such chromatin organization may provide a gene-regulatory network underlying cell type-specific gene expression.
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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 | 0.024 | 0.151 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.004 | 0.004 |
| Bibliometrics | 0.005 | 0.003 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.008 | 0.005 |
| Open science | 0.006 | 0.004 |
| Research integrity | 0.018 | 0.007 |
| Insufficient payload (model declined to judge) | 0.110 | 0.051 |
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".