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Record W4379058175 · doi:10.1016/j.celrep.2023.112583

Pyruvate metabolism controls chromatin remodeling during CD4+ T cell activation

2023· article· en· W4379058175 on OpenAlexaff
Enric Mocholí, Laura Russo, Keshav Gopal, Andrew G. Ramstead, Sophia M. Hochrein, Harmjan R. Vos, Geert Geeven, Adeolu Adegoke, Anna T. Hoekstra, Robert M. van Es, José M. Ramos Pittol, Sebastiaan J. Vastert, Jared Rutter, Timothy R. D. J. Radstake, Jorg van Loosdregt, Celia R. Berkers, Michal Mokrý, Colin C. Anderson, Ryan M. O’Connell, Martin Vaeth, John R. Ussher, Boudewijn Burgering, Paul J. Coffer

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHistone Deacetylase Inhibitors Research
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsCell biologyPyruvate dehydrogenase complexChromatin remodelingHistoneAcetyl-CoAP300-CBP Transcription FactorsPyruvate dehydrogenase kinaseChemistryBiologyHistone acetyltransferaseT cellBiochemistryMetabolismHistone AcetyltransferasesEnzymeGeneImmunology

Abstract

fetched live from OpenAlex

Upon antigen-specific T cell receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming. Here, we show that the generation of extramitochondrial pyruvate is an important step for acetyl-CoA production and subsequent H3K27ac-mediated remodeling of histone acetylation. Histone modification, transcriptomic, and carbon tracing analyses of pyruvate dehydrogenase (PDH)-deficient T cells show PDH-dependent acetyl-CoA generation as a rate-limiting step during T activation. Furthermore, T cell activation results in the nuclear translocation of PDH and its association with both the p300 acetyltransferase and histone H3K27ac. These data support the tight integration of metabolic and histone-modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation. Targeting this pathway may provide a therapeutic approach to specifically regulate antigen-driven T cell activation.

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 score0.017
Threshold uncertainty score0.739

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 head0.010
GPT teacher head0.253
Teacher spread0.243 · 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

Citations39
Published2023
Admission routes1
Has abstractyes

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