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Record W4220783087 · doi:10.1083/jcb.202104022

GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression

2021· article· en· W4220783087 on OpenAlexafffund
Gregory C. Addicks, Hongbo Zhang, Dongryeol Ryu, Goutham Vasam, Alex E. Green, Philip Marshall, Sonia Patel, Baeki E. Kang, Doyoun Kim, Elena Katsyuba, Evan G. Williams, Jean‐Marc Renaud, Johan Auwerx, Keir J. Menzies

Bibliographic record

VenueThe Journal of Cell Biology · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsUniversity of Ottawa
FundersGuangzhou Municipal Science and Technology ProjectEuropean Research CouncilCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaMinistry of Science and ICT, South KoreaMinistry of Science ICT and Future PlanningSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Research Foundation of KoreaNatural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of ChinaÉcole Polytechnique Fédérale de Lausanne
KeywordsAcetylationZinc fingerYY1BiologyCell biologyP300-CBP Transcription FactorsTranscription factorLysineBiochemistryChemistryGene expressionHistone AcetyltransferasesGeneAmino acidPromoter

Abstract

fetched live from OpenAlex

Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme general control of amino acid synthesis protein 5 (GCN5; KAT2A) in regulating muscle integrity by inhibiting DNA binding of the transcription factor/repressor Yin Yang 1 (YY1). Here we report that a muscle-specific mouse knockout of GCN5 (Gcn5skm-/-) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. GCN5 was found to acetylate YY1 at two residues (K392 and K393), disrupting the interaction between the YY1 zinc finger region and DNA. These findings were supported by human data, including an observed negative correlation between YY1 gene expression and muscle fiber diameter. Collectively, GCN5 positively regulates muscle integrity through maintenance of structural protein expression via acetylation-dependent inhibition of YY1. This work implicates the role of protein acetylation in the regulation of muscle health and for consideration in the design of novel therapeutic strategies to support healthy muscle during myopathy or aging.

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 score0.003

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)0.0010.000

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 head0.008
GPT teacher head0.256
Teacher spread0.247 · 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

Citations15
Published2021
Admission routes2
Has abstractyes

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