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Record W3111845758 · doi:10.1016/j.stemcr.2020.11.005

TINC— A Method to Dissect Regulatory Complexes at Single-Locus Resolution— Reveals an Extensive Protein Complex at the Nanog Promoter

2020· article· en· W3111845758 on OpenAlexaff
Anja S. Knaupp, Monika Mohenska, Michael R. Larcombe, Ethan Ford, Sue Mei Lim, K. C. Y. Wong, Joseph Chen, Jaber Firas, Cheng Huang, Xiaodong Liu, Trung Viet Nguyen, Yu Sun, Melissa L. Holmes, Pratibha Tripathi, Jahnvi Pflueger, Fernando J. Rossello, Jan Schröder, Kathryn Davidson, Christian M. Nefzger, Partha Pratim Das, Jody J. Haigh, Ryan Lister, Ralf B. Schittenhelm, José M. Polo

Bibliographic record

VenueStem Cell Reports · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversity of ManitobaResearch Institute in Oncology and HematologyCancerCare Manitoba
FundersAustralian Research CouncilMedical Research CouncilNational Health and Medical Research CouncilState Government of VictoriaAustralian GovernmentStem Cells AustraliaHoward Hughes Medical Institute
KeywordsBiologyHomeobox protein NANOGChromatinEpigenomeNanog Homeobox ProteinEmbryonic stem cellGenePromoterTranscription factorComputational biologyGeneticsPsychological repressionRegulation of gene expressionEpigeneticsTranscriptional regulationCell biologyGene expressionDNA methylationInduced pluripotent stem cell

Abstract

fetched live from OpenAlex

Cellular identity is ultimately dictated by the interaction of transcription factors with regulatory elements (REs) to control gene expression. Advances in epigenome profiling techniques have significantly increased our understanding of cell-specific utilization of REs. However, it remains difficult to dissect the majority of factors that interact with these REs due to the lack of appropriate techniques. Therefore, we developed TINC: TALE-mediated isolation of nuclear chromatin. Using this new method, we interrogated the protein complex formed at the Nanog promoter in embryonic stem cells (ESCs) and identified many known and previously unknown interactors, including RCOR2. Further interrogation of the role of RCOR2 in ESCs revealed its involvement in the repression of lineage genes and the fine-tuning of pluripotency genes. Consequently, using the Nanog promoter as a paradigm, we demonstrated the power of TINC to provide insight into the molecular makeup of specific transcriptional complexes at individual REs as well as into cellular identity control in general.

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 score0.063
Threshold uncertainty score0.796

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 head0.025
GPT teacher head0.294
Teacher spread0.269 · 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

Citations15
Published2020
Admission routes1
Has abstractyes

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