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Record W4416612091 · doi:10.1016/j.isci.2025.114206

NF-κB-dependent GR cistrome redistribution recruits GR to inflammatory genes but correlates with lesser glucocorticoid-mediated repression

2025· article· en· W4416612091 on OpenAlexafffund
Mahmoud Mostafa, Amandah Necker‐Brown, Alex Gao, Andrew Thorne, Akanksha Bansal, Lucy Swift, Sarah K. Sasse, Pina Colarusso, Anthony N. Gerber, Robert Newton

Bibliographic record

VenueiScience · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEstrogen and related hormone effects
Canadian institutionsUniversity of Calgary
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchCumming School of Medicine, University of CalgaryUniversity of Calgary
KeywordsPsychological repressionGeneGlucocorticoid receptorTranscription factorRegulation of gene expressionGlucocorticoidRedistribution (election)Transcription (linguistics)

Abstract

fetched live from OpenAlex

While ligand-activated glucocorticoid receptor (GR) binds DNA to activate transcription, glucocorticoids, including budesonide, reduce inflammatory gene expression, yet recruit GR to many such gene loci. In epithelial cells, the inflammatory cytokine, interleukin-1β (IL1B), activates nuclear factor (NF)-κB to induce gene expression, and co-treatment with budesonide produces nanoscale GR-RELA nuclear co-localization. Such co-stimulation orchestrated reciprocal genome-wide redistribution of GR- and RELA-binding regions (GBRs and RBRs, respectively) relative to each mono-treatment to produce widespread GBR-RBR overlap. This correlated with increased RNA polymerase-2 presence and required NF-κB for GR cistrome remodeling. Mapping transcription start sites to the nearest GBR or RBR each revealed associations with upregulated, but not repressed, genes. Importantly, RBR proximity to budesonide-upregulated genes and GBR proximity to IL1B-upregulated genes correlated with attenuated repression on co-treatment. As this occurred on a background of glucocorticoid-induced repression, GR presence at specific IL1B-induced gene loci may reduce/protect from an otherwise more prevalent glucocorticoid-induced repression.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.005
GPT teacher head0.243
Teacher spread0.238 · 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 source (direct Gemma or distilled Codex), 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

Citations3
Published2025
Admission routes2
Has abstractyes

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