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Record W4200147207 · doi:10.1038/s41421-021-00344-4

Histone lysine methacrylation is a dynamic post-translational modification regulated by HAT1 and SIRT2

2021· article· en· W4200147207 on OpenAlexafffund
Kyle Delaney, Minjia Tan, Zhesi Zhu, Jinjun Gao, Lunzhi Dai, Sun‐Joo Kim, Jun Ding, Maomao He, Levon Halabelian, Lu Yang, Prabakaran Nagarajan, Mark R. Parthun, Sangkyu Lee, Saadi Khochbin, Y. George Zheng, Yingming Zhao

Bibliographic record

VenueCell Discovery · 2021
Typearticle
Languageen
FieldMedicine
TopicSirtuins and Resveratrol in Medicine
Canadian institutionsStructural Genomics ConsortiumCanada Research ChairsUniversity of Toronto
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesGenentechInstitut National Du CancerFondation ARC pour la Recherche sur le CancerWellcome TrustAgence Nationale de la RechercheNovartis PharmaOntario Genomics InstituteNational Cancer InstituteEuropean Federation of Pharmaceutical Industries and AssociationsNational Institutes of HealthU.S. Department of Health and Human ServicesOntario GenomicsGenome CanadaFundação de Amparo à Pesquisa do Estado de São PauloInstitut pour la Recherche en Santé PubliqueMcGill UniversityUniversity of ChicagoPfizer
KeywordsHistoneLysineEpigenomeSIRT2Histone methyltransferaseHistone codeAcetylationHistone H2ABiochemistryHistone H3ChemistryBiologySirtuinGeneGene expressionAmino acidNucleosomeDNA methylation

Abstract

fetched live from OpenAlex

Histone lysine crotonylation is a posttranslational modification with demonstrated functions in transcriptional regulation. Here we report the discovery of a new type of histone posttranslational modification, lysine methacrylation (Kmea), corresponding to a structural isomer of crotonyllysine. We validate the identity of this modification using diverse chemical approaches and further confirm the occurrence of this type of histone mark by pan specific and site-specific anti-methacryllysine antibodies. In total, we identify 27 Kmea modified histone sites in HeLa cells using affinity enrichment with a pan Kmea antibody and mass spectrometry. Subsequent biochemical studies show that histone Kmea is a dynamic mark, which is controlled by HAT1 as a methacryltransferase and SIRT2 as a de-methacrylase. Altogether, these investigations uncover a new type of enzyme-catalyzed histone modification and suggest that methacrylyl-CoA generating metabolism is part of a growing number of epigenome-associated metabolic pathways.

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 head0.008
GPT teacher head0.277
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 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

Citations56
Published2021
Admission routes2
Has abstractyes

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