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Record W2048387831 · doi:10.1371/journal.pone.0077020

Solution NMR Structure and Histone Binding of the PHD Domain of Human MLL5

2013· article· en· W2048387831 on OpenAlexafffund
Alexander Lemak, Adelinda Yee, Hong Wu, Damian Yap, Hong Zeng, L. Dombrovski, Scott Houliston, Samuel Aparício, C.H. Arrowsmith

Bibliographic record

VenuePLoS ONE · 2013
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related gene regulation
Canadian institutionsOntario Institute for Cancer ResearchBC Cancer AgencyUniversity of TorontoUniversity Health NetworkStructural Genomics Consortium
FundersNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of CanadaOntario GenomicsNational Institutes of HealthMinistero dello Sviluppo EconomicoOntario Ministry of Economic Development and InnovationOntario Genomics InstituteCanadian Institutes of Health ResearchGenome CanadaWellcome TrustGlaxoSmithKlinePfizerEli Lilly and Company
KeywordsHistone H3HistonePHD fingerChromatinBiologyProtein domainH3K4me3Histone methyltransferaseBiochemistryComputational biologyCell biologyDNAZinc fingerGene expression

Abstract

fetched live from OpenAlex

Mixed Lineage Leukemia 5 (MLL5) is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. In addition to its catalytic domain, MLL5 contains a PHD finger domain, a protein module that is often involved in binding to the N-terminus of histone H3. Here we report the NMR solution structure of the MLL5 PHD domain showing a variant of the canonical PHD fold that combines conserved H3 binding features from several classes of other PHD domains (including an aromatic cage) along with a novel C-terminal α-helix, not previously seen. We further demonstrate that the PHD domain binds with similar affinity to histone H3 tail peptides di- and tri-methylated at lysine 4 (H3K4me2 and H3K4me3), the former being the putative product of the MLL5 catalytic reaction. This work establishes the PHD domain of MLL5 as a bone fide 'reader' domain of H3K4 methyl marks suggesting that it may guide the spreading or further methylation of this site on chromatin.

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 score0.020
Threshold uncertainty score0.183

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 head0.015
GPT teacher head0.222
Teacher spread0.207 · 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

Citations32
Published2013
Admission routes2
Has abstractyes

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Same venuePLoS ONESame topicCancer-related gene regulationFrench-language works237,207