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Record W2771290324 · doi:10.1038/s41467-017-02259-9

H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1

2017· article· en· W2771290324 on OpenAlex
Renata Z. Jurkowska, Qin Su, Goran Kungulovski, W. Tempel, Yanli Liu, Pavel Bashtrykov, Judith Stiefelmaier, Tomasz P. Jurkowski, Srikanth Kudithipudi, Sara Weirich, Raluca Tamas, Hong Wu, L. Dombrovski, P. Loppnau, Richard Reinhardt, Jinrong Min, Albert Jeltsch

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related gene regulation
Canadian institutionsStructural Genomics ConsortiumUniversity of Toronto
FundersNational Institute of General Medical SciencesOffice of ScienceMinistero dello Sviluppo EconomicoDeutsche ForschungsgemeinschaftNational Natural Science Foundation of ChinaOntario Ministry of Economic Development and InnovationNovartis PharmaOntario Genomics InstituteNational Cancer InstituteEuropean Federation of Pharmaceutical Industries and AssociationsWellcome TrustFundação de Amparo à Pesquisa do Estado de São PauloGenome CanadaOntario GenomicsPfizerArgonne National LaboratoryU.S. Department of Energy
KeywordsMethylationHistoneHistone H3Gene silencingBiologyAcetylationBinding siteGeneticsMolecular biologyGene

Abstract

fetched live from OpenAlex

SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2. Mutations in the K14ac/K9me binding sites change the sub-nuclear localization of 3TD. ChIP-seq analyses show that SETDB1 is enriched at H3K9me3 regions and K9me3/K14ac is enriched at SETDB1 binding sites overlapping with LINE elements, suggesting that recruitment of the SETDB1 complex to K14ac/K9me regions has a role in silencing of active genomic regions.

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.

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 score0.425
Threshold uncertainty score0.277

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 science0.0010.000
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 head0.015
GPT teacher head0.326
Teacher spread0.311 · 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