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Record W4200565535 · doi:10.1038/s41467-021-27077-y

Androgen receptor and MYC equilibration centralizes on developmental super-enhancer

2021· article· en· W4200565535 on OpenAlexafffund
Haiyang Guo, Yiming Wu, Mannan Nouri, Sándor Spisák, Joshua W. Russo, Adam G. Sowalsky, Mark M. Pomerantz, Wei Zhao, Keegan Korthauer, Ji-Heui Seo, Liyang Wang, Seiji Arai, Matthew L. Freedman, Housheng Hansen He, Shaoyong Chen, Steven P. Balk

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity of British Columbia
FundersNational Cancer InstituteInstitutes of Biomedical Sciences, Fudan UniversityTerry Fox Research InstituteCanadian Institutes of Health ResearchChina Scholarship CouncilCanadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of CanadaMinistry of Education of the People's Republic of ChinaCanadian Centre for Applied Research in Cancer ControlUniversity of PittsburghNational Institutes of HealthU.S. Department of Health and Human ServicesFudan UniversityU.S. Department of Defense
KeywordsAndrogen receptorEnhancerBiologyComputational biologyCell biologyGeneticsTranscription factorGeneCancerProstate cancer

Abstract

fetched live from OpenAlex

Androgen receptor (AR) in prostate cancer (PCa) can drive transcriptional repression of multiple genes including MYC, and supraphysiological androgen is effective in some patients. Here, we show that this repression is independent of AR chromatin binding and driven by coactivator redistribution, and through chromatin conformation capture methods show disruption of the interaction between the MYC super-enhancer within the PCAT1 gene and the MYC promoter. Conversely, androgen deprivation in vitro and in vivo increases MYC expression. In parallel, global AR activity is suppressed by MYC overexpression, consistent with coactivator redistribution. These suppressive effects of AR and MYC are mitigated at shared AR/MYC binding sites, which also have markedly higher levels of H3K27 acetylation, indicating enrichment for functional enhancers. These findings demonstrate an intricate balance between AR and MYC, and indicate that increased MYC in response to androgen deprivation contributes to castration-resistant PCa, while decreased MYC may contribute to responses to supraphysiological androgen therapy.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.296
Threshold uncertainty score0.343

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 studies0.0000.000
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 head0.018
GPT teacher head0.293
Teacher spread0.275 · 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

Citations79
Published2021
Admission routes2
Has abstractyes

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