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Record W2043057770 · doi:10.1101/gad.236794.113

The methyltransferase G9a regulates HoxA9-dependent transcription in AML

2014· article· en· W2043057770 on OpenAlex
Bernhard Lehnertz, Caroline Pabst, Le Su, Michelle Miller, Feng Liu, Lin Yi, Regan Zhang, Jana Krošl, Eric Yung, Jeanette Kirschner, Patty Rosten, T. Michael Underhill, Jian Jin, Josée Hébert, Guy Sauvageau, R. Keith Humphries, Fábio Rossi

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

VenueGenes & Development · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsBC Cancer AgencyUniversité de MontréalInstitute for Research in Immunology and CancerUniversity of British Columbia
FundersNational Institute of General Medical SciencesNational Institute of Mental HealthCanadian Institutes of Health ResearchNational Institutes of Health
KeywordsBiologyMyeloid leukemiaCancer researchTranscription factorStem cellMethyltransferaseHaematopoiesisHistone methyltransferaseEpigeneticsCell biologyProgenitor cellLeukemiaMethylationImmunologyGeneticsGene

Abstract

fetched live from OpenAlex

Chromatin modulators are emerging as attractive drug targets, given their widespread implication in human cancers and susceptibility to pharmacological inhibition. Here we establish the histone methyltransferase G9a/EHMT2 as a selective regulator of fast proliferating myeloid progenitors with no discernible function in hematopoietic stem cells (HSCs). In mouse models of acute myeloid leukemia (AML), loss of G9a significantly delays disease progression and reduces leukemia stem cell (LSC) frequency. We connect this function of G9a to its methyltransferase activity and its interaction with the leukemogenic transcription factor HoxA9 and provide evidence that primary human AML cells are sensitive to G9A inhibition. Our results highlight a clinical potential of G9A inhibition as a means to counteract the proliferation and self-renewal of AML cells by attenuating HoxA9-dependent transcription.

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 score0.270
Threshold uncertainty score0.396

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 head0.007
GPT teacher head0.217
Teacher spread0.209 · 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