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Record W3148170352 · doi:10.1101/2021.03.27.437301

Dynamic phase separation of the androgen receptor and its coactivators to regulate gene expression

2021· preprint· en· W3148170352 on OpenAlexaff
Fan Zhang, Samantha Wong, Joseph Lee, Shreyas Lingadahalli, C A Wells, Neetu Saxena, C. Antonio Sánchez, Bei Sun, Ana Karla Parra-Nuñez, Novia Chan, Jennifer M. Bui, Yuzhuo Wang, Paul S. Rennie, Nathan A. Lack, Artem Cherkasov, Martin Gleave, Jörg Gsponer, Nada Lallous

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsCanada's Michael Smith Genome Sciences CentreUniversity of British Columbia
Fundersnot available
KeywordsAndrogen receptorActivator (genetics)Transcription factorCompartmentalization (fire protection)Transcription (linguistics)AndrogenCell biologyBiologyProstate cancerGeneCancer researchChemistryHormoneEndocrinologyGeneticsCancerEnzymeBiochemistry

Abstract

fetched live from OpenAlex

Abstract Numerous cancers, including prostate cancer (PCa), are addicted to transcription programs driven by superenhancers (SEs). The transcription of genes at SEs is enabled by the formation of phase-separated condensates by transcription factors and co-activators with intrinsically disordered regions. The androgen receptor (AR), main oncogenic driver in PCa, contains large disordered regions and is co-recruited with the co-activator MED1 to SEs to promote oncogenic programs. In this work, we show that dynamic AR-rich, liquid-like foci form in PCa models upon androgen stimulation and correlate with AR transcriptional activity. The co-activator MED1 plays an essential role in the formation of AR foci while AR antagonists hinder their formation. These results suggest that enhanced compartmentalization of AR and co-activators at SEs may play an important role in the activation of oncogenic transcription programs in PCa. A better understanding of the assembly and the regulation of these AR-rich compartments may provide novel therapeutic options.

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 score0.002
Threshold uncertainty score0.006

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.010
GPT teacher head0.267
Teacher spread0.256 · 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

Citations12
Published2021
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicRNA Research and SplicingFrench-language works237,207