MétaCan
Menu
Back to cohort
Record W4283026547 · doi:10.1101/gad.349489.122

Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the <i>Sox2</i> locus

2022· article· en· W4283026547 on OpenAlexafffund
Tiegh Taylor, Natalia Sikorska, Virlana M. Shchuka, Sanjay Chahar, Chenfan Ji, Neil Macpherson, Sakthi D. Moorthy, Marit A. C. de Kort, Shanelle Mullany, Nawrah Khader, Zoe E. Gillespie, Lida Langroudi, Ian C. Tobias, Tineke L. Lenstra, Jennifer A. Mitchell, Tom Sexton

Bibliographic record

VenueGenes & Development · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsCanada Research ChairsUniversity of Toronto
FundersH2020 European Research CouncilAgence Nationale de la RechercheNational Human Genome Research InstituteInstitute of GeneticsNational Institutes of HealthOncode InstituteCanadian Institutes of Health ResearchKWF KankerbestrijdingCanada Foundation for InnovationInstitut National de la Santé et de la Recherche MédicaleOntario Ministry of Research and InnovationNatural Sciences and Engineering Research Council of CanadaEuropean Commission
KeywordsBiologyChromatinLocus (genetics)GeneticsArchitectureSOX2Regulation of gene expressionComputational biologyTranscription factorEvolutionary biologyCell biologyGene

Abstract

fetched live from OpenAlex

How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter–enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream from the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, partial disruption of promoter–enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 transcription. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.921
Threshold uncertainty score0.508

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.005
GPT teacher head0.180
Teacher spread0.175 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations51
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueGenes & DevelopmentSame topicGenomics and Chromatin DynamicsFrench-language works237,207