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Record W2921990867 · doi:10.15252/embr.201643260

KMT1 family methyltransferases regulate heterochromatin–nuclear periphery tethering via histone and non‐histone protein methylation

2019· article· en· W2921990867 on OpenAlexaff
Radhika Rao, Alhad Ashok Ketkar, Neelam Kedia, Vignesh K Krishnamoorthy, Vairavan Lakshmanan, Pankaj Kumar, Abhishek Mohanty, Shilpa Dilip Kumar, Sufi O. Raja, Akash Gulyani, Chandra Prakash Chaturvedi, Marjorie Brand, Dasaradhi Palakodeti, Shravanti Rampalli

Bibliographic record

VenueEMBO Reports · 2019
Typearticle
Languageen
FieldMedicine
TopicTelomeres, Telomerase, and Senescence
Canadian institutionsOttawa Hospital
FundersNational Centre for Biological SciencesThe Wellcome Trust DBT India AllianceDepartment of Biotechnology, Ministry of Science and Technology, IndiaIndian Council of Medical ResearchDirectorate for Biological SciencesTata Institute of Fundamental ResearchWellcome Trust
KeywordsHeterochromatinHistone methyltransferaseHeterochromatin protein 1EZH2EuchromatinHistone methylationBiologyMethyltransferaseHistoneMethylationCell biologyDNA methylationGeneticsChromatinGene expressionDNAGene

Abstract

fetched live from OpenAlex

Euchromatic histone methyltransferases (EHMTs), members of the KMT1 family, methylate histone and non-histone proteins. Here, we uncover a novel role for EHMTs in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone methylation. We show that EHMTs methylate and stabilize LaminB1 (LMNB1), which associates with the H3K9me2-marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates heterochromatin anchorage at the NP We further demonstrate that the loss of EHMTs induces many hallmarks of aging including global reduction of H3K27methyl marks and altered nuclear morphology. Consistent with this, we observe a gradual depletion of EHMTs, which correlates with loss of methylated LMNB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defects in aged cells. Collectively, our work elucidates a new mechanism by which EHMTs regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.593
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.010
GPT teacher head0.260
Teacher spread0.250 · 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.

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

Citations23
Published2019
Admission routes1
Has abstractyes

Explore more

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